Guidelines On Second-Line and Alternative First-Line ART For Adults and Adolescents May 2013 - 0

Table of Contents
Chapter
Acronyms and Abbreviations.............................................................................................. 3
Introduction and Preamble................................................................................................. 5
Section I: Technical Guidelines............................................................................................ 7
First Line & Second Line ART Regimen................................................................. 7
Substitution vs. Switch.......................................................................................... 7
Alternative ARV Drugs For Intolerance to ZDV/TDF
and NVP/EFV: Substitution................................................................................... 9
Monitoring Patients on First Line ART for Failure................................................. 12
Identifying Treatment Failure............................................................................... 13
Protocol for determining ART failure
(Protocol A1.1) at ART centers.............................................................................. 16
Management Protocol based on SACEP decision and
Viral load test Results........................................................................................... 19
Initiating the standardized NACO Second-Line Regimen............................................ 21
Drug Interaction:.................................................................................................. 23
Second-Line ART and TB Treatment..................................................................... 25
Laboratory monitoring of patients on Second Line Regimen............................... 27
Adherence and Second-Line ART.......................................................................... 27
Section II: Operational Guidelines....................................................................................... 31
State AIDS Clinical Expert Panel (SACEP).............................................................. 31
Eligibility and criteria for provision of Second Line ART....................................... 34
Protocol for SACEP review.................................................................................... 34
TOR of additional manpower: SACEP coordinator................................................ 36
Section III: M & E Tools........................................................................................................ 39
Instructions for Monitoring/records Keeping for Second Line ART...................... 39
Section IV: Laboratory Guidelines....................................................................................... 45
Introduction:......................................................................................................... 45
Intended Use of HIV-1 PVL Assay in ACOs
Second Line ART Initiative:................................................................................... 45
Techniques of HIV 1 PVL Assay:......................................................................... 48
Plasma Viral Load Assays currently in use
in NACOs Second-Line Roll Out:........................................................................... 49
Specimen Collection, Storage, and Transportation............................................... 51
Factors to be considered while Interpreting the Viral Load Results:.................... 55
Limitation of Viral Load Assays:............................................................................ 56
National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013 1
Standardization of HIV-1 Plasma Viral Load Reporting............................................... 56
Quality Assurance for HIV-1 Plasma Viral Load Testing:............................................. 57
Operational Plan for HIV-1 Viral Load Testing and EQAS...................................... 59
Precautions and Specific Instructions for Reagents and Equipments................... 61
Troubleshooting.................................................................................................... 63
DBS collection for all patients undergoing Viral Load Testing.................................... 63
Annexure
Annex I......................................................................................................................... 67
Annex II................................................................................................................. 71
Annex III................................................................................................................ 73
Annex IV............................................................................................................... 74
Annex V................................................................................................................ 78
Annex VI............................................................................................................... 79
Annex VII (a) Viral Load Test Requisition Form ................................................. 81
Annex VII (b) COBASAmplicor Reporting Format............................................... 82
Annex VII (c) Taqman Reporting Format............................................................ 83
Annex VII (d) Viral Load Result Form, Amplicor HIV Monitoring, v1.5............... 84
Annex VIII............................................................................................................. 85
Annex IX Second Line Reporting........................................................................ 88
1 SL + AL: SACEP Register for Alternative First Line &
Second Line ART (Adults and Children)....................................................... 88
2 AL: Alternative First Line Format for SACEP
Meeting (Adult & Children)......................................................................... 90
2 SL: Second Line Format for
SACEP Meeting (Adult & Children )............................................................. 92
3AL + SL Combined Monthly Reporting
Format for Second & Alternative First Line ART.......................................... 94
4 AL: List of patients on Alternative First Line ART...................................... 100
4 SL: List of Patients on Second Line ART.................................................... 101
5 SL: Centre Wise (Linked Centre Information)
break up for PLHIV Initiated on Second Line ART.................................... 102
Annexure X........................................................................................................... 103
Acknowledgements.............................................................................................................. 105
2 National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013
Acronyms and Abbreviations
3TC Lamivudine
ABC Abacavir
AIDS Acquired Immunodeficiency Syndrome
ART Antiretroviral Therapy
ARV Antiretroviral
ATV Atazanavir
AZT/ZDV Zidovudine
bPI Boosted PI
CD4 count CD4+ T-Lymphocyte
COE Centers of Excellence
d4T Stavudine
ddI Didanosine
EC Enteric Coated
EFV Efavirenz
FDC Fixed-Dose Combination
FTC Emtricitabine
Hb Hemoglobin
HIV Human Immunodeficiency Virus
IDV Indinavir
LPV Lopinavir
NACEP National AIDS Clinical Expert Panel
NFV Nelfinavir
NNRTI Non-Nucleoside Reverse Transcriptase Inhibitor
NRTI Nucleoside Reverse Transcriptase Inhibitor
NVP Nevirapine
PI Protease Inhibitor
PLHIV People Living with HIV
/r Low-Dose Ritonavir
RTV Ritonavir
SACEP State AIDS Clinical Expert Panel
SQV Saquinavir
TDF Tenofovir Disoproxil Fumarate
VL Viral Load
Introduction and Preamble
The National ART programme launched on 1st April 2004 in eight government hospitals
in six high prevalence states has since been scaled up to 400 ART centres where in
a total of around 16,00,000 patients have been registered in HIV care and nearly
6,00,000 patients are currently on ART. The national programme provides free First
line, alternate First line and Second line antiretroviral drugs to adults and children as
per their eligibility.
A Technical Resource Group (TRG) on ART has been constituted at NACO that meets
regularly to update and formulate the technical guidelines for First line and Second line
ART. All ART centers in the country have access to Second line ART but for initiation of
Second line ART around 41 centers have been identified. These include 10 Centres of
Excellence, 7 Pediatric Centres of Excellence and 20 ART Plus centers. This is to ensure
that only those who have confirmed failure to First line ART are initiated on Second
line treatment thereby minimizing unnecessary switches. Besides this, a special
training of health care providers at all ART centers is done on monitoring patients
initiated on antiretroviral therapy along with regulatory mechanisms to minimize the
chances of resistance due to irrational prescriptions. In order to ensure high quality of
care, to ensure that only eligible patients are started on Second line ART and maintain
uniformity in treatment, State Clinical Expert Panels (SACEP) have been constituted at
all CoEs and ART plus centers where Second line ART is initiated. Every patient that is
referred to these centers with a suspected failure to First line ART is First reviewed by
SACEP and, if the suspected treatment failure is confirmed by Viral load testing, then
eligible patients are initiated on Second line ART after adequate preparedness. After
the patients become stable on Second line ART, they are transferred back to their
referring ART centre. They continue to get their Second line drugs at their own ART
center thereafter. Also complicated cases that need further review and opinion are
referred to National AIDS Clinical Expert Panel (NACEP) at NACO.
The initial roll out of Second line ART was done at 2 Centers of Excellence:
Government Hospital of Thoracic Medicine (GHTM), Tambaram and Sir JJ Hospital,
Mumbai. During the pilot phase, only those patients who were on ART at these
centers for at least 6 months were considered for Second line ART. The experience
gained at these two centers during the pilot phase was used for further modification
and refinement of protocols. Currently, Second line ART is initiated at 10 Centers
of Excellence, 7 Pediatric Centers of Excellence and 20 ART plus centers. All ART
centers in the country are linked to these CoE/ART plus centers and a well-defined
referral procedure is in place.
Section I: TECHNICAL GUIDELINES
1.1 First LINE & Second LINE ART REGIMEN:
The working definition of First and Second Line ART Regimen is as follows:
First-line ART:
First-line ART is the initial regimen prescribed for an ART nave patient when the
patient fulfills national clinical and laboratory criteria to be initiated on ART.
(Current NACO treatment guidelines for First-line ART recommend three drug
combination therapy from two classes of ARV drugs for initial treatment i.e. 2 NRTI
+ 1 NNRTI)
Second-line ART:
Second-line ART is the subsequent regimen used in sequence immediately after
First-line therapy has failed.
(Current NACO treatment guidelines recommend use of Ritonavir-boosted protease
inhibitors (bPIs) supported by two agents from the NRTI class, of which at least one
should be new.
1.2 SUBSTITUTION VS. SWITCH
Change of ARVs prescribed should be carefully distinguished between substituting a

drug within a given regimen and switching an entire ART regimen:
Treatment Failure refers to the loss of antiviral efficacy to current regimen

and it triggers the SWITCH of the entire regimen from First to Second line. It
is identified by clinical and/or immunological and confirmed by the virological
criteria.
Single drug replacement of individual ARV (usually within the same class) for
toxicity, drug-drug interactions, or intolerance refers to SUBSTITUTION of
individual drug and which does not indicate a Second line regimen is being
used.
The following ART regimens have been designated as National ART regimen by National
AIDS Control Organization. (Table 1)
Table 1: NACO Approved ART regimen
Regimen ARV Drug Combinations Indications
Zidovudine + Lamivudine First line Regimen for patients with Hb 9 gm/dl and not on
Regimen I
+ Nevirapine concomitant ATT
Tenofovir + Lamivudine + First line Regimen for patients with Hb<9 gm/dl and not on
Regimen I (a)
Nevirapine concomitant ATT
Zidovudine + Lamivudine First line Regimen for patients with Hb 9 gm/dl and on
Regimen II
+ Efavirenz concomitant ATT
First line Regimen for patients with Hb<9 gm/dl and on
concomitant ATT
Tenofovir + Lamivudine + First line for all patients with Hepatitis B and /or Hepatitis C
Regimen II (a)
Efavirenz co-infection
First line Regimen for pregnant women, with no exposure to
sd-NVP in the past
Regimen for patients on AZT Containing First line regimen,
who develop toxicity to both NVP and EFV
Zidovudine + Lamivudine
Regimen III
+ Atazanavir/Ritonavir Also Second line regimen for those who are on TDF contain-
ing First line regimen if Hb 9 gm/dl
For patients of Regimen III who develop severe Atazanavir
toxicity
Zidovudine + Lamivudine
Regimen III (a)
+ Lopinavir/Ritonavir First line regimen for patients with HIV-2 infection with Hb
9 gm/dl
Second line regimen for those who are on AZT/d4T contain-
ing regimen in the First line
Tenofovir + Lamivudine+
Regimen IV
Atazanavir/Ritonavir Also for patients on TDF containing First line regimen who
develop toxicity to both NVP and EFV
For patients on Regimen IV who develop severe Atazanavir
toxicity
Tenofovir + Lamivudine+
Regimen IV (a) First line Regimen for patient with HIV 2 infection with Hb
Lopinavir/Ritonavir
< 9 gm/dl
First line Regimen for all women exposed to sd-NVP in the past
Stavudine+ Lamivudine+ Second line for those who are on TDF containing regimen in
Regimen V
Atazanavir/Ritonavir the First line if Hb< 9 gm/dl
Stavudine+ Lamivudine+ For patients on Regimen V who develop severe Atazanavir

Regimen V (a)
Lopinavir/Ritonavir toxicity
Patients on EFV due to concomitant ATT need to be substituted with NVP two weeks
after completion of ATT or in the next clinic visit. No lead in dose for NVP required
in such patients.
If NVP is discontinued for > 2 weeks, while re-starting NVP, one has to use a lead-in
dose for 2 weeks.
Patients on AZT based regimen to be substituted with TDF, if they develop anaemia.
For patients with TDF toxicity, use AZT containing regimen if not anaemic, d4T if
anaemic (e-approval from SACEP required for d4T as supply of d4T is limited).
If AZT, d4T and TDF cannot be used, refer to SACEP at CoE only. For established 3TC
toxicity, refer to SACEP at CoE only. SACEP can take a decision to provide alternative
drug and inform NACEP or can ask NACEP, if opinion is required.
Patients who have developed AZT induced anaemia in the past should not be re
challenged with AZT again.
Patients who developed severe NVP hypersensitivity (SJS and TEN) in the past should
not be re-challenged with NVP again.
1.3 ALTERNATIVE ARV DRUGS FOR INTOLERANCE TO ZDV/TDF AND NVP/EFV:

SUBSTITUTION
Substitution of ARV drugs for reasons of intolerance or toxicity or drug-drug interactions
may be needed in following cases:
Intolerance to both ZDV and TDF: in this case, d4T based treatment may be an alternative
(e-approval from SACEP required for d4T as supply of d4T is limited).
Intolerance to both NVP and EFV: in this case, ATV/r as a substitution ARV will be provided
upon review and approval by the SACEP.
As per NACO ART Guidelines for Adults and Adolescents, as a general principle, mild
toxicities (grade 1 and 2), do not require discontinuation of ART or drug substitution.
Symptomatic treatment may be given. Moderate or severe toxicities (grade 3 and 4) may
require substitution of the drug with another ARV of the same class. (Table 2)
Table 2: Major Toxicities caused by First-line ARVs Regimen and recommended drug
substitutions
Regimen Toxicity Drug substitution

ZDV/3TC/ ZDV related persistent GI intolerance Substitute with TDF
NVP or severe hematological toxicity Substitute with EFV (except in preg-
NVP related severe hepatotoxicity nancy.
NVP related severe rash (but not In this situation, switch to LPV/r)
life-threatening) Substitute with bPIs
NVP-related life threatening rash
(Stevens Johnson Syndrome, angio
-edema)
ZDV/3TC/EFV ZDV related persistent GI intolerance Substitute with TDF
or severe hematological toxicity Substitute with NVP, if not on concom-
EFV related persistent CNS toxicity itant ATT or there is no contraindica-
tion to NVP use. bPI (ATV/r) is recom-
mended in such circumstances
TDF Usually well tolerated Symptomatic management of minor
+3TC+NVP/ Minor: weakness and lack of energy, side effects
EFV headache, diarrhea, nausea, vomit- Vitamin D3, Bisphosphonates, and
ing and intestinal gas Calcium supplements may be used in
TDF can reduce bone mineral density patients with osteoporosis
Renal dysfunction (Check urine for as per NACO lab monitoring protocol
routine/microscopic , blood urea, Substitute with AZT, if Hb 9 gm/dl;
creatinine every 6 months) otherwise, substitute with d4T follow-
Renal dysfunction is usually mild, ing review & e-approval by SACEP
asymptomatic
Reverses when stop medication
Acute renal failure (rare): reduce
dose when renal failure or if severe
toxicity, substitute
ATV Indirect hyperbilirubinaemia, clinical Seek SACEP/NACEP guidance on
jaundice, prolonged PR interval- First substitution with LPV/r.
degree, symptomatic AV block in
some patients, hyperglycemia, fat
mal distribution, possible increased
bleeding episodes in people with
haemophilia, nephrolithiasis
Notes:
The general principle is that single drug substitution for toxicity should be made
within the same ARV class e.g. substitution of TDF with AZT or d4T (for renal
toxicity or anemia) or EFV with NVP (for CNS toxicity or in pregnancy).
d4T should not be a part of HAART for ART naive patients. Patients who are on d4T,
substitution should be done with AZT or TDF depending on Hb. Substituting d4T
may not reverse lipodystrophy but may slow its progression.
If a life-threatening toxicity occurs, all ART should be stopped until the toxicity has
resolved and a revised regimen commenced when the patient has recovered.
The triple NRTI regimen has been shown to be inferior in its outcome and is not used
in the National programme
Table 3: Substituting with alternative First Line ARV drugs
First line ARV causing the toxicity Alternative substitute Remarks
(a) Intolerance to both TDF and AZT

Patient should have been tried on ZDV and TDF with documented intolerance to both.
d4T+3TC will be provided after review and e-approval by the SACEP
TDF + 3TC d4T + 3TC Continue the same NNRTI

ZDV + 3TC
(either NVP or EFV)
(b) For intolerance to both NVP and EFV
Patient should have been tried on both NVP and EFV (except for if history of Steven John-
son Syndrome, exfoliative dermatitis, erythema multiform or toxic epidermal necrolysis is
present) and documented as not tolerating, before requiring substitution for the NNRTI
component.
NVP or EFV ATV/r Continue with the same NRTI backbone i.e.
ZDV/3TC or TDF/3TC if no problems
Essentially this moves the patient to the PI-based regimen. Counsel for good adherence. If this regimen
fails, there is no other optimal alternative regimen at present in the National programme.
These patients should be referred to the SACEP for review, then COE shall manage and
provide ATV/r as substitution for intolerance to NNRTI.
(c) Intolerance to TDF, d4T and AZT
Refer such cases to SACEP at CoE for review and ABC based ARV, if required
See Annex I: Severity grading of clinical and laboratory toxicities of ARVs
1.4 MONITORING PATIENTS ON First LINE ART FOR FAILURE
Good adherence is the key to maintaining the First line ART for longer duration.
Good adherence is required for Second line ART to ensure viral suppression and
increase survival.
The principles of monitoring patient on First line ART are:
Clinical monitoring and staging at each visit as per NACO guidelines.
o Do clinical staging at each visit: use the T staging for clinical events. (see
Table 4 below)
Immunological monitoring: Ensuring the routine monitoring lab tests are done eg.
CD4 count every 6 months (or even earlier depending on CD4 value/clinical judgment).
Adherence support and monitoring to ensure >95% adherence:

Check for progress of improvement at each visit and weight.
Screen for TB: ask for symptoms and signs of TB e.g. fever, weight loss, night sweats,
haemoptysis, lymph nodes in neck etc.
Determine if Cotrimoxazole is required or not, based on CD4 counts and WHO
Clinical staging.
Development of a new or recurrent WHO Clinical stage 4 condition while on ART for at least
6 months is considered functional evidence of the progression of HIV disease. However,
certain WHO stage 3 conditions like pulmonary TB and severe bacterial infections may
signify treatment failure whereas certain WHO stage 4 conditions like TB lymphadenitis,
uncomplicated pleural TB, esophageal candidiasis and recurrent bacterial pneumonias may
not indicate treatment failure which needs to be taken into consideration. If the patient
doesnt improve following institution of appropriate treatment for these stage 4 conditions,
they should be promptly referred to SACEP. (see below)
Table 4: Clinical staging events to guide decision making on switching
New or recurrent
Recommendations Additional Management Options
event on ARTa
Asymptomatic Do Not switch Maintain schedule follow-up visits,
(T1) regimen including CD4 monitoring (if available)
Continue to offer adherence support
Stage 2 event (T2) Do Not switch Treat and dmanage staging event
regimenb Access and offer adherence support
Check if on treatment for at least six months
Assess continuation of reintroduction of OI
prophylaxis
Schedule earlier visit for clinical review and
consider CD-4 (if available)c
New or recurrent
Recommendations Additional Management Options
event on ARTa
Stage 3 event (T3) Consider switching Treat and manage staging event and
regimenbd monitor response
Assess and offer adherence support
Check CD4 cell count (if available)cd
prophylaxis
Stage 4 event (T4) Switching regimenbe Treat and manage staging event and monitor
response
prophylaxis
Check CD4 cell count (if available)c
Assess and other adherence support
a Refers to clinical stages while on ART for at least six months (termed T1, T2, T3, T4).
b Differentiation of opportunistic infections from immune reconstitution inflammatory syndrome is necessary.
c Treat and manage the staging event before measuring CD4 cell count.
d Certain WHO clinical stage 3 conditions (e.gpulmonary TB, severe bacterial infections) may be indicators of tratment
failure and thus require consideration of Second-line therapy; response to appropriate therapy should be used to
evaluate the need for switching of therapy.
e Some WHO clinical stage 4 conditions (lymph node TB, uncomplicated TB pleural disease, oesophageal candidiasis,
recurrent bacterial pneumonia) may not be indicators of treatment failure and thus do not require consideration of
Second-line-therapy, response to appropriate antimicrobial therapy should be used to evaluate the need to switch therapy.
TB can occur at any CD4 level and does not necessarily indicate ART failure. The response to
TB therapy should be used to evaluate the need to switch ARV drugs. In the case of pulmonary
TB and some types of extrapulmonary TB (e.g simple lymph node TB or uncomplicated pleural
disease), the response to TB therapy is often good and the decision to switch ARV drugs can
be postponed and monitoring can be stepped up. This also applies if severe and/or recurrent
bacterial infections (as stage 3 or 4 events) or oesophageal candidiasis respond well to therapy.
1.5 IDENTIFYING TREATMENT FAILURE
High index of suspicion is required

Look for the following evidence of suspected treatment failure among patients on First line ART (en
sure patient has been on First line ART for at least 6 months):
New OIs/recurrence/clinical events after 6 months on First line ART( after ruling out IRIS).
Progressive CD4count decline.
Slow/no clinical improvement over 6-12 months, associated with stationary CD4, despite
good adherence.
Clinical deterioration in spite of good adherence to therapy.
* Even though one is less likely to develop IRIS after 6 months of therapy.
The NACO definitions of ART failure are listed in table 5 below:
Table 5: Definitions of Clinical, Immunological, and Virological treatment failure for First-
line regimen.
Clinical failure (i) New or recurrent WHO stage 4 condition, after at

least 6 months on ART (ii, iii)
Immunological failure Fall of CD4 count to pre- therapy baseline (or below)
50% fall from the on- treatment peak value (if known)
Persistent CD4 levels below 100 cells/mm3 (iii, iV)
Virological failure Plasma viral load > 5,000 copies/ml3 (vi)
Notes:
i. Current event must be differentiated from IRIS.
ii. Certain WHO clinical stage 3 conditions ( eg pulmonary TB, severe bacterial
infections) may indicate treatment failure and thus require Second line therapy
to be considered.
iii. Some WHO stage 4 conditions (lymph node TB, uncomplicated TB pleural
disease, oesophageal candidiasis, recurrent bacterial pneumonia) may not
indicate treatment failure and thus Second line therapy need not be considered.
iv. Some experts consider persistent CD4 counts of below 50 cells/mm3 after
12 months of ART to be more appropriate.
v. Switch of treatment should be done only when the viral count is more than
5,000 cells/mm3.
At the ART center, suspicion of treatment failure depends on good clinical assessment
backed up by use of regular CD4 counts. Before labeling a person as having failure
ensure that the following has been done:
Patient had a reasonable trial of First line ART for (at least 6 months)
Assess adherence and support patient to improve this (reinforce)
Screen and treat intercurrent OIs, exclude IRIS
Provide Cotrimoxazole based on CD4 or clinical stage immediately
If TB is present: assess if this is re infection or IRIS or a new infection. If the response

to TB therapy is good, then the decision to switch therapy can be postponed and the
patient re-evaluated again.
CD4 count (most recent) latest by a month after treating the intercurrent illness, if any.
The Second line ART will be initiated only at CoE/pCoE/ART plus centers after SACEP
review and patients will be transferred back to their referring center after 6 months viral
load testing (except those having an OI at 6th month or toxicity to ART drugs).
In order to minimize the unnecessary referral to SACEP, the referring ART centre should
follow the following guidelines before referring patients to SACEP:-
1) It is important to differentiate between complications of HIV disease and ARV

toxicities as these may present with similar signs and symptoms.
2) The inter-current illnesses like Hepatitis-A, Malaria, etc. must be kept in mind as
they may also lead to symptoms similar to ARV drugs toxicities.
3) Toxicities due to other drugs used concurrently like Cotrimoxazole, anti-TB drugs,
other antibiotics, herbal or other medications etc. must be ruled out before the
toxicities are thought to be due to ARV.
4) As a general principle, mild toxicities do not require discontinuation of ART or

substitution with alternative First line drugs. Symptomatic treatment may be given
if toxicity is mild and patient monitored closely.
5) Moderate to severe toxicities require substitution with a different drug of same

class with a different toxicity profile. A grading of common lab and clinical toxicities
is at Annex I.
6) Severe life threatening toxicities e.g. Stevens Johnson syndrome require

discontinuation of all ARV drugs until patient is stabilized.
7) History and nature of toxicities to ARV drugs must be clearly documented in the patient
record, and where possible objective grading of toxicities should be done according
to Annexure I. Photo documentation of skin rash & mucosal lesions, lipodystrophy
etc. should be done at the ART Centre and must be sent during SACEP referral.
All ART centers shall use protocol A1.1 listed below before referring patients to their linked
CoE/ART plus centre as a case of suspected treatment failure.
1.6 PROTOCOL FOR DETERMINING ART FAILURE
(PROTOCOL A1.1) AT ART CENTERS
Suspect treatment failure during the medical consultation on following ground:

Clinical: occurrence of new OI or malignancy, signifying clinical disease progression; recurrence
of previous OI, onset or recurrence of WHO stage IV (& certain stage III) conditions
CD4: fall of CD4 count to pre-therapy baseline without other concomitant infection to explain
transient CD4 count decrease/50% fall from on-treatment peak value/persistent CD4 level < 100
cells/mm3
YES
Patient has NO Signs or symptoms of OI

been on ART for at
Manage IRIS or OI, especially TB
least 6 months
YES
Work with patient to resolve issues causing non-adherence
Continue 1st line ART, give OI prophylaxis if necessary.
NO Follow-up monthly. Reassess clinically.
Does Patient adhere
properly to 1st line ART Repeat CD4 after 1 month (to confirm validity and exclude lab and
physiological variability)
If CD4 not declining, continue adherence support and repeat CD4
in 3 months. Reassess and determine if treatment failure.
YES
Most recent CD4 Repeat CD4 immediately

NO
within 1 month of current Perform clinical staging
medical consultation Give prophylaxis and/or treatment for OI
available
YES
Does CD4 value

indicate treatment NO Rule out other causes e.g. IRIS.
failure? As per 3 Continue 1st line ART and support adherence
criteria above
YES
Review need for OI prophylaxis/treatment especially CPT

Explain to patient about suspicion of treatment failure and need to refer to SACEP review
Continue 1st line ART while waiting for SACEP review.
Refer to SACEP for appointment dates by email (given 2 alternate appointment dates) - inform patient of
date and to attend SACEP in person with all records.
Send all patient information/records to SACEP/COE/ART Plus Centre.
Do not stop First line ART till virological failure confirmed and Second line ART started.
Patients who are referred to SACEP for review should be accompanied with complete
details of the history and all records, recent CD4 and other baseline tests, photographs of
skin/mucosal lesions, if any. Incomplete records will delay decisions to be taken by SACEP.
A referral format is enclosed at Annex II
Eligibility for enrollment into Second Line Treatment:
All patients who require Second line ART shall be reviewed by SACEP at COE/pCoE/
ART Plus centres as per laid down referral procedure, irrespective of the fact whether
they started treatment in private sector or NACO centres.
The SACEP review will be based on the referral from the ART centre providing First
line ART to the patient suspected of treatment failure.
Each COE/pCoE/ART Plus Centre will have defined ART centres linked to it and pa-
tients from these centres only will be reviewed by a particular CoE/pCoE/ART plus
center after proper referral.
When a patient is suspected to have treatment failure, the ART centre must follow the NACO
protocol 1.1) before referring to the SACEP. This is to ensure that appropriate referrals for
suspect treatment failure are made:
Laboratory tests including Hb, LFT, RFT and CD4 and other symptom-directed testing
should be done immediately if suspected of treatment failure. There should not a
big gap between these tests and SACEP referral
Most recent CD4 count (within 1 month) of the current medical consultation should
be available
In the meanwhile, the patient is to be counseled for 100% adherence in a few

sessions (and/or be optionally linked to the nearest Care and support Centre for
adherence support)
Ensure use of Cotrimoxazole prophylaxis if CD4 < 250 cell/mm3 or based on WHO
Clinical staging
Continue with the 1st line ART regimen during this time.
If OI or any intercurrent illness is present, treat for the specific OIs. If the OI treatment
is not available in the institution then these patients can be referred to the nearest
Government hospital or COE/pCoE/ART Plus Centre for further management.
Counsel and support adherence during this period of OI treatment as some patients
may not adhere to taking ART when they feel ill.
For suspected TB, refer to RNTCP services for treatment and monitor the response
to TB therapy. If the response to TB therapy is good, the patient should be evaluated
again for suspicion of treatment failure. Repeat CD4 counts 2 weeks after the OI has
been treated, and for TB after the intensive phase (i.e. 8 weeks of ATT completed).
Review the patient for suspected treatment failure as per protocol.
If protocol 1.1 points towards a suspected treatment failure, following steps need to be
taken:
The referring ART centre will inform and counsel the patient on the findings of
suspected treatment failure, support psychosocial needs, counsel to continue
1st line ART until otherwise advised by the ART SMO/MO; and with the informed
consent of the patient for shared confidentiality initiate the process for referral to
the SACEP for COE/pCoE/ART Plus Centres.
During counseling/while referring, never tell the patient that his First line has failed
until viral load report is available as failed. Counsel about suspicion of failure and
that he is being referred for opinion and confirmation.
The ART center will send the request form with the filled details together with a
confirmed contact phone of the patient; and photocopies of the case sheets/patient
treatment record to the COE/ART Plus Centre by e-mail.
The CoE/ART plus centre will enter the patient details in the SACEP register and
review the referral form with other clinical details.
After review of patient records by the SACEP coordinator/research fellow/SMO,

if the SACEP at CoE/pCoE/ART plus centre considers that the patient should be
reviewed by SACEP then two alternative appointment dates are given by e-mail to
the referring centre who will inform the patient.
After review and other necessary investigations by the SACEP, the CoE/pCoE/ART
plus centre will send the feedback form (lower half of the referral form) to the
referring centre and inform them about the final decision of the SACEP.
If the patient is to be started on 2nd line ART, the CoE/pCoE/ART plus centre will ask
the referring centre to transfer out the patient to that particular CoE/pCoE/ART plus
centre and patient may be sent back before 6 month (may be at 3 month) to Nodal
ART Centre on request, if clinically stable and improving
1.7 MANAGEMENT PROTOCOL BASED ON SACEP DECISION AND VIRAL LOAD
TEST RESULTS
Once patient has been referred to SACEP for evaluation according to the technical protocol
(A1.2), the SACEP will review the patient with his record and document its decision, which
can be
o Provide 2nd line ART
o Not eligible for 2nd line ART
o Continue First line, reinforce adherence and re-evaluate
o Evaluate for HIV 2
After the decision of the SACEP to provide 2nd line ART to the patient, the COE staff will
ensure the necessary work to prepare the patient for initiation of Second line ART.
The SACEP coordinator/Data Manager shall communicate the decision of the SACEP to the
referring ART centre for their reference, and ART centre to transfer out the patient to COE/
pCoE/ART plus Centre. (See M&E section). The center shall ensure baseline laboratory and
clinical screening is done and recorded before initiation of Second line ART. As a part of
Treatment preparedness, the patient should undergo a minimum of 3 counseling sessions.
Treatment supporter should ideally be present. Consent form for 2nd line ART initiation
should be signed by the patient ANNEX III
The CoE/pCoE/ART plus center shall also ensure linkage with NGO/CBO/FBO/positive
network/Care and Support Centre/ICTC for outreach and community/home based care
Only the Programme Director/nodal officer of the COE/pCoE/ART plus Centre are
authorized to prescribe Second-line ARVs after approval of SACEP. The decision to switch
from First line to Second line therapy resides on the decision of the SACEP which will meet
every Tuesday (or the designated day of the centre), to review the case history, order the
Viral load testing and approve initiation of Second line ART for treatment failure and use of
alternative regimens.
Details in the reporting and recording formats should be completed by the COE/ART plus
Centre staff so that good documentation is present. This will enable the COE/ART plus
Centre and the national programme to learn from the national rollout of Second line ART.
Routine drug resistance testing is not part of the national protocol for Second-line ART,
however it may be done for research/surveillance and monitoring purposes. Blood samples
on dried blood spots (DBS) shall be collected and stored for use at a later date for drug
resistance genotyping. (See Laboratory guidelines section below)
Protocol A1.2: SACEP Management according to viral load results
Suspect treatment failure by clinical and/or CD4 criteria

(Exclude other factors: poor adherence, intercurrent illness, TB, OIs, IRIS etc.)
Viral load test
VL VL 400 VL
< 400 copies/ml 5,000 Copies/ml >5,000 Copies/ml
No change in 1st No change in 1st Virologically confirmed treatment failure.

line ART line ART Switch to 2nd line ART regimen
Review patient clinically. Continue 1st line ART Transfer out from referring center to CoE/
Investigate for other causes for clinical signs or CD4 fall. pCoE/ART plus center
Evaluate for OI/IRIS/non-HIV related conditions Counsel patient for 2nd line ART (minimum 3
Reinforce adherence to 1st line ART. sittings) preparedness and adherence.
Screen for OIs/TB.
Give cotrimoxazole if required.
Investigate and correct anaemia.
SACEP refers patient back Continue ART at Initiate 2nd line ART when patient is prepared.
to original ART center referring (original)
with appointment date for ART Centre
next evaluation/VL test Repeat CD4 and VL
at 6 months with written FU at COE/pCoE/ART Plus Centre for at least 6
in 3 months then
treatment plan and feedback months to stabilize patient and adherence to 2nd
SACEP review
form. line ART, review the 6-month VL
Counsel positive
Counsel positive prevention, condom use and
Monthly follow-up at ART prevention,
nutrition
centre. condom usage and
nutrition
Reinforce adherence VL after 6 months
Strict CD4 follow-up3 of II nd line therapy
monthly to monitor CD4
trend and if CD4 criteria VL < 400 VL > 400
for failure is not there CD4
follow up is enough.
Counsel positive prevention,
condom use and nutrition Transfer back to If VL > 400 with no
original (referring) OI, still transfer the
ART center with patient back to the
In 5-10% of the patients, there may be discordance treatment plan, referring centre
between the Viral load and the clinical assessment/CD4. on case-to-case and call the patient
It has been noted in some cases, VL < 400 copies/ml or VL basis depending back for VL testing
is 400-5,000 copies/ml but the patients have clinical events on capacity of after next 6 months
and CD4 is decreasing. Such cases should be documented referring ART or else retain the
and sent to NACO for expert opinion (NACEP). centre patient, if required
1.8 INITIATING THE STANDARDIZED NACO SECOND-LINE REGIMEN
After the SACEP has approved Second line ART for the patient, the clinical management shall
be the responsibility of the COE/pCoE/ART Plus Centre and the patient will be Transferred
out from the referring ART centre to the COE/pCoE/ART Plus Centre.
The objective of the Second-line is:
To prolong survival of the PLHIV
The NACO standard Second line regimen (TDF + 3TC + ATV/r) (for those on AZT/d4T
in First line regimen) aims to achieve viral suppression for as long as possible, so
that survival can be prolonged.
Under the public health settings in India, the objective of the Second-line is to prolong
survival of the PLHIV rather than a complete viral suppression as in developed countries
where multiple Second line options and salvage regimen are available and early switching
is the norm. The NACO technical resource group on ART had extensive discussions on the
regimen which is optimum for the national setting and on early vs late switching as well.
Since we had only one Second line regimen with no salvage regimen, it was decided to go
for late switching to give the benefit of First line ART for as long as possible.
Table 6: NACO Second Line Regimen:
ARV drugs for

Dosage Dosing schedule
2nd line
TDF + 3TC Fixed dose combination of Please advise the patients to
Tenofovir 300 mg + Lamivudine consume all the three pills
300 mg simultaneously after meal
once daily in tablet form (preferably dinner). (Keep the
drug interactions in mind)
ATV/r Tab. Atazanavir 300mg, Tab. Ritona-
vir 100 mg
Each tab to be taken once daily
simultaneously
The major side effects of Second line ART are described below in Table 7.
Table 7: Side effects related to the NACO Second Line Regimen:
ARV drug Side effect/toxicity Management

TDF Usually well tolerated Symptomatic management of
minor side effects
Minor: weakness and lack of energy, headache,
diarrhea, nausea, vomiting and intestinal gas. Monitor Liver and Renal function
test as per NACO lab monitoring
More serious side effects include liver or protocol
kidney failure and pancreas disease.
Calcium supplements may be used
TDF can reduce bone mineral density in patients with osteoporosis
ATV* Apart from the PI-class specific side-effects like The patients need to be counselled
hyperglycemia, fat maldistribution, hyperlipi- that they may appear to be jaun-
daemia (especially with Ritonavir boosting), in- diced with yellow eyes but they
creased bleeding episodes in hemophiliacs etc. should not be afraid as it will be a
the unique side-effects of Atazanavir include cosmetic problem only (like Gilbert
indirect hyperbilirubinaemia (producing yellow disease). It should not be taken as
discoloration of eyes), skin rash and nephroli- hepatotoxicity. However, LFT has to
thiasis (rare). be done should someone appears
to have jaundice. Also, they should
Unique drug interaction involving Atazanavir: be advised to consume plenty of
water.
In addition to all the drug interactions involving
PI class, Atazanavirhas significantdrug interac- Antacid: Give Atazanavir at least
tion with antacids, H2 Receptor antagonists 2 hours before or 1 hour after
and proton pump inhibitors* antacids or any buffered medications.
LPV/r Side effects include abdominal pain, abnormal Symptomatic management of minor
stools or bowl movements, diarrhea, feeling side effects.
weak/tired, headache and nausea. In addition,
patients taking Lopinavir should be monitored Supportive counseling and use of
for possible liver problems. People taking the other drugs to manage GI effects
drug who have liver disease, such as hepatitis should be done. These symptoms
B or hepatitis C, may experience a worsening improve after a few weeks.
of their liver condition. A small number of pa-
Monitor LFTs, Lipid profile and
tients have experienced severe liver problems.
blood sugar regularly
3TC Usually well tolerated
Side effects may include cough, diarrhea,

dizziness, headache, loss of appetite, mild
stomach cramps or pain and trouble sleeping. Symptomatic management of
minor side effects
More serious side effects include burning,
tingling, or pain in the hands, arms, feet, or
legs; chills; ear, nose, or throat problems;
fever; muscle aches; nausea; pale skin; severe
stomach pain; skin rash; unusual tiredness or
weakness; vomiting; and yellow eyes or skin.
CAUTION : (WE SHOULD BE CAUTIOUS IN RECOMMENDING THE USE OF H2RA & PPIs
WITH ATV/r AS MOST OF OUR PATIENTS ARE ARV-EXPERIENCED; THIS IS A BLACK BOX
WARNING FOR ATV; ONLY SYSTEMIC ANTACIDS CAN BE CO-PRESCRIBED)
Side-effects of Atazanavir: Apart from the PI-class specific side-effects like hyperglycaemia,
fat maldistribution, hyperlipidaemia (especially with Ritonavir boosting); the unique side-
effects of Atazanavir includeindirect hyperbilirubinaemia (producing yellow discolouration
of eyes), skin rash, prolongation of PR interval and nephrolithiasis.
1.9 DRUG INTERACTION:
Avoid concurrent use of the following drugs:
Astemizole, Cisapride, Fluticasone, Indinavir, Lovastatin, Simvastatin, Midazolam,

Terfenadineetc
Unique drug interaction involving Atazanavir:
In addition to all the drug interactions involving PI class, Atazanavir has significant drug
interaction with antacids, H2 Receptor antagonists and proton pump inhibitors.
Patient on following
S No Recommendation/points to remember for ATV
drugs concomitantly
1 Antacids Give ATV at least 2 hours before or 1 hour after antac-
ids or buffered medications
2 H2 Receptor Antagonist 1. H2 receptor antagonist dose should not exceed a
dose equivalent to Famotidine 40 mg BID in ART-
nave patients or 20 mg BID in ART-experienced pa-
tients.
2. Give ATV 300 mg + RTV 100 mg simultaneously with

and/or >10 hours after the H2 receptor antagonist.
Example:If a PLHIV onZidovudine + Lamivudine + Ata-

zanavir/Ritonavir(Regimen IV) requires to be treated
with Famotidine 20 mg BID or Ranitidine 150 mg BID,
S/he should be instructed to take Tab. Famotidine/Ra-
nitidine withZidovudine + Lamivudine at 8.00 AM and
in evening give ZL and ATV/r at 8 p.m. and ensure that
there is a gap of at least 2 hours before or 1 hour after
Famotidine/Ranitidine evening dose.
Patient on following
S No Recommendation/points to remember for ATV
drugs concomitantly
3 Proton pump Inhibitor 1. H2 receptor antagonist is not recommended with
Tenofovir + Lamivudine +Atazanavir/Ritonavir
2. PPIs should not exceed the dose of Omeprazole

20 mg daily or equivalent dose of Esomeprazole
20mg/Pantoprazole 40 mg/Rabeprazole 20 mg in
PI-nave patients, along with Ritonavir boosted
Atazanavir.PPIs should be administered at least 12
hours prior toAtazanavir/Ritonavir.
3. PPIs are not recommended in PI-experienced

patients.
Example: If a PLHIV is onTenofovir + Lamivudine +

Atazanavir/Ritonavir requires to be treated with PPI,
S/he should be instructed to take Tab. Omeprazole 20
mg/Esomeprazole 20mg/Pantoprazole 40 mg/Rabe-
prazole 20 mg OD at 8 AM andTenofovir + Lamivudine
+Atazanavir/Ritonavirafter 8 PM.
a. Prolongation of P-R and Q-Tcinterval in the ECG can occur. So PR interval needs to be
monitored in patients with known conduction defects or with concurrent use of other
drugs that alter conduction abnormalities (like diltiazem, clarithromycin, cisapride,
ketoconazole etc.). However, routine ECG before starting Atazanavir based ART is not
mandatory.
b. Atazanavir induced urolithiasis is also reported; presumably due to precipitation of the

drug resulting in crystalluria in a manner analogus to Indinavir.
c. If the serum total Bilirubin is > 7 mg/dl or the Child-Pugh Score is 7, then ATV/Ritonavir
cannot be used and the details of such cases should be mailed to National AIDS Clinical
Expert Panel (NACEP).
Counseling issues:
There is a need for enhanced counseling of the PLHIV on these regimens particularly unique
side effects of Atazanavir/Ritonavir.
So, the patients need to be counseled that they may appear to be jaundiced with yellow
eyes but they should not be afraid as it is only a cosmetic problem. It should not be taken
as hepatotoxicity. However, LFT has to be done should someone appears to have jaundice.
Also, they should be advised to consume plenty of water.
As we are using the ATV and RTV as separate pills, during counseling we need to impress
upon the patients to take both the pills together as our patients are going to take ATV,
RTV along with TDF, if they miss RTV, then there will be decreased ATV blood level and it
may lead to treatment failure. So during the counseling session, these points need to be
stressed adequately. They should also be counselled that ATV/r should always be taken on
a full stomach as otherwise the absorption of ATV goes down.
All the Nodal Officers, SMOs & MOs are requested to sensitize the counselors, pharmacists,
nurse and other ART Centre staff on use of Atazanavir/Ritonavir.
Important consideration in pregnancy
Ritonavir booster Lopinavir (not ATV) is to be used for pregnant women exposed to sd- NVP
in the past
1.10 SECOND-LINE ART AND TB TREATMENT
Tuberculosis is the most commonly detected serious opportunistic infection among PLHIVs
in India. While tuberculosis has to be treated appropriately and on priority, in the context
of Second-line ART drug-drug interactions must to be considered. Rifampicin alters the
metabolism of Protease Inhibitors, including Lopinavir, Atazanavir and Ritonavir, and reduces
effectiveness of standard doses. However, Rifamycin-class drugs are highly efficacious in
treatment of tuberculosis. Annex V
Another Rifamycin, Rifabutin, can be administered in the presence of PI-containing Second

line ART regimen without compromising the efficacy of ART or Anti TB treatment. Therefore
NACP and RNTCP have recommended the substitution of Rifabutin for Rifampicin for the
duration of TB treatment. In the presence of the boosting drug like Ritonavir (PI), Rifabutin
metabolism is altered, and less Rifabutin is needed than would be without Ritonavir.
Therefore, the dosage of Rifabutin during the administration of Second line regimen
containing LPV/r shall be 150 mg thrice weekly for all patients, weighing >30 kg weight. The
remainder of the TB treatment regimens, including dosing and duration, remain unchanged
as per RNTCP guidelines.
As with all anti-TB treatment, supervised treatment under DOTS is required. The patients
DOTS provider should be informed and counseled regarding the substitution using Rifabutin,
by the treating medical officer.
Rifabutin dose: 150 mg OD, three times a week
Some of the common side effects of Rifabutin include orange- brown discoloration of skin,
tears, saliva, sweat, urine, and stools and will stop when you finish taking Rifabutin. The
ART centre SMO/MO should be contacted in case of h/o chest pain, muscle aches, severe
headache, fatigue, sore throat, flu-like symptoms, vision changes, unusual bruising or
bleeding, nausea/vomiting, yellowing of the skin or eyes.
Initiation of 2nd line ART in patient already on anti-TB treatment
If a patient is already on anti-TB treatment, and needs to be initiated on Second-line ART,

then substitute Rifabutin for Rifampicin within the RNTCP regimen for 2 weeks prior to
initiation of Second-line ART. This is to allow hepatic metabolism (induced by Rifampicin)
to normalize prior to initiation of PI-containing regimens. While the patient is counseled
and prepared for initiation of 2nd line regimen, the patient should still be given the 1st line
ART regimen. There is no need to increase the dose of EFV with Rifabutin containing ATT
RNTCP recording and reporting: TB treatment categorization does not change with the use of
Rifabutin, which is a simple substitution for Rifampicin. The substitution of Rifabutin for Rifampicin
should be noted on the TB treatment card, and in the TB register Remarks column.
Initiation of Anti-TB treatment in patients already on 2nd line ART
If the patient is already on 2nd line ART (Atazanavir/Ritonavir containing treatment protocol),
and detected to have TB, subsitute Rifabutin for Rifamipicin within the category I or II anti-
TB regimen from the start of TB treatment.
In regards to the availabilty of Rifabutin at the DOTS centres a joint letter has been issued by
DDG (TB) and DDG (NACO) dated, 19th Feb 2013. The letter is enclosed at Annex X.
Initiation of Second line ART/Anti TB Treatment in the presence of TB co-infection

(Protocol A 1. 3)
PLHIV on 1st line ART reviewed by SACEP, has
treatment failure and eligible for 2nd line ART
Already on category I or II Need to initiate Patient already on

Anti-TB treatment 2nd line ART with 2nd line and then
With or without concurrent detection detected to have TB
EFV-based ART regimen of TB co-infection co-infection
Substitute with Rifabutin

for Rifampicin, within the
anti-TB treatment regimen
Treatment preparedness &
After 2 weeks counseling Treatment
of Rifabutina preparedness &
Initiate Rifabutin containing
counseling
Anti-TB regimen on priority
Treatment preparedness Initiate Rifabutin
& counseling Initiate 2nd line ART regimen
containing Anti-TB
when patient is stabilized on
Initiate 2nd line ART regimen on priority
TB treatment after 2 weeks
Note:
a The 2 week period allows hepatic function to normalize after induction of P450 cytochrome enzymes
by Rifampicin
b Patient to be counseled well for both anti-TB and 2nd line ART. Pill burden is high. If patient is not started on 2nd
line ART immediately, then continue 1st line regimen till patient is switched to switch to 2nd line ART occurs.
1.11 LABORATORY MONITORING OF PATIENTS ON SECOND LINE REGIMEN
The protocol for laboratory monitoring of patients on Second line ART is described in
table 9 below
Table 9: Protocol for laboratory monitoring of patients on Second line ART
Base-line
Tests 3 6 12 18 24
0
Hb, CBC Then annually
LFT
Renal function test Then every
6 -monthly
Fasting blood sugar Then annually
Fasting lipid profile
Viral Load (VL) Then no more VL unless indicated in
protocol A1.2
CD4
More frequently if required.
Note: Resistance testing is for operational research/surveillance/monitoring only, under
current national programme.
A baseline and annual checkup of fasting blood sugar and lipid profile is recommended. This is
to understand the baseline and monitor the possible morbidities/side effects of PIs. However,
the national programme will not be providing statins or fibrates for treatment of dyslipidemia.
1.12 ADHERENCE AND SECOND-LINE ART
NACO 2008 tools to support counseling and treatment adherence for all patients and
especially for patients who have difficulty with their First line ART and those taking
Second line ART:
1. Patient counseling diary (individual)
2. Use the Visual Analogue Scale (VAS) to help understand drug adherence
3. Patient education information leaflets for their prescribed regimens
4. Patient pill-taking monthly calendar
Long term adherence continues to be challenge to PLHIV taking lifelong ART. The most
common reason for HIV drug resistance is due to non-adherence and missed doses.
Adherence approaching 100% is required for optimal viral suppression both in First line and
Second line ART.
The experience of the national programme to date is that in general, socio-demographic
characteristics such as age, sex, social class, marital status or personality traits, race, religion
and educational levels are poor predictors of adherence. Patients beliefs, knowledge and
expectations (sometimes shared by friends and community), strongly influence medical
decision-making and willingness to begin and then adhere to prescribed treatments.
Adherence is found to be greater when the person perceives the need for treatment,
believes the treatment will be helpful and understands the purpose of the medications.
Attitudes of friends, trust in physicians and confidence in ones own ability to follow the
agreed-upon treatments are also associated with adherence. Lack of belief in the efficacy of
treatment may lead to either treatment refusal, or inadequate adherence once initiated.
It is for this reason that the initial detailed counseling by the doctor about combination
therapy is crucial for later success. Simply telling the patient that its time to begin antiviral
therapy, writing out prescriptions and handing them to a patient who asks no questions
and expresses no opinions is likely to lead to adherence problems and treatment failure.
Occasionally, well-meaning physicians urge reluctant patients to start treatment, despite
the patients reservations. The more assertive patient may state that he or she is not ready
to start, but others may acquiesce to a regimen that they consider of doubtful value or not
compatible with their life circumstances. Do not start Second line ART if the patient is not
ready to comply with adherence and follow up schedule.
HIV/AIDS is associated with neurocognitive problems such as memory loss. This will cause
adherence problems. Some patients may have trouble sorting their pills for the day or
the week, while others may have trouble keeping track of the time, or may simply forget.
Even among asymptomatic patients, memory problems are present. When memory is a
significant problem, prescription of complex medical regimens is unlikely to succeed unless
social (e.g., family member) or institutional (e.g., home attendant) resources are regularly
available to help with the scheduling and taking of medications.
Psychiatric disorders also may constitute barriers to adherence. Even mild conditions such as
depressed mood, as elicited on self-report rating scales, may be associated with medication
non-adherence, either because of impaired concentration, which is one of the criteria for
diagnosing mood disorders, or because of feelings of hopelessness and despair. Among
those with chronic and severe psychiatric disorders, noncompliance with psychotropic
medication often contributes to relapse. When substance abuse is also present in HIV-
infected patients with severe mental illness, many of whom live alone in unstable housing,
the probability of effective management of combination therapy is poor.
Two-way communication between the clinical team and patient is critical to the success
of adherence. The patient has to believe that combination therapy will make a profound
difference in extending life, or else the regimens burdens will outweigh the perceived
rewards. Initiating combination therapy is not usually regarded as an immediate need. If
it takes extra time, or additional visits, for the clinical team to convince the patient that
combination therapy should be initiated now, or for the patient to convince the doctor
that his or her current life circumstances are simply not conducive to starting now, then
extra time must be provided. However, there are a few urgent situations when immediate
initiation may be considered imperative. One example is a patient with an essentially
untreatable condition such as PML who is rapidly getting sicker. In these cases, ART can
lead to life-saving remission. In less urgent situations, treatment can be safely put off while
doctor-patient discussions continue.
At the outset, before even beginning combination therapy, it is helpful to review anticipated
problems and barriers to adherence, which then permits the patient to work out solutions
on his or her own or with assistance. For this purpose, some providers give their patients
1-2 weeks of cotrimoxazole and to use this time to reinforce adherence. Which doses
are problematic? What are the circumstances? What is the patient thinking when errors
occur? What is the patients attitude about mistakes? Does he consider a fifteen-minute
delay a catastrophe signifying irremediable failure? Alternatively, what do they think about
missing a weekends worth of medications? Such rehearsal is often extremely helpful in
anticipating and correcting potential pitfalls.
Some patients find it helpful to have a written treatment plan that shows the name of the
medication, time of each dose, number of pills or capsules per dose and meal restrictions,
if any, along with a telephone number to call with questions and for the next appointment
date. Both doctor and patient should keep a copy of the plan for review at the next visit.
Other techniques for promoting adherence include identifying daily activities that can be
linked to pill-taking (e.g., a regular TV show), keeping a medication diary or log (preprinted
forms can be prepared), preparing pills for the week at fixed times (e.g., Sunday evening),
and otherwise relating pill-taking to the normal rhythms of daily life. Planning ahead for
changes in routine or for weekends can forestall lapses at such times.
Mechanical aids are often useful. These range from pill boxes with dividers in which
medications can be sorted by the week and time of day to timers, alarms, beepers that can
be set to ring when it is time to take pills, to signs and checklists posted on refrigerators.
Social assistance can make a major difference, especially at the beginning of the regimen.
Some people have a family member/treatment supporter who agrees to provide reminders
every time medication is scheduled. Children remind their mothers; sometimes mothers
remind their adult children.
Over time, initial enthusiasm can dwindle as the incessant demands of scheduling persist.
As people feel better and return to work, new problems arise. Among these are maintaining
confidentiality, arranging schedules to accommodate pill-taking, frequent trips to the
bathroom (if taking medication that requires a high liquid intake), occasional days with
significant side effects such as diarrhoea, the constant reminder of illness and simply the
ongoing burden of the regimen. It is important to know in more detail about the hurdles,
questions and worries that arise over time with ART, and accordingly to develop individual
interventions to maintain adherence once therapy is established.
For patients who have difficulties with adherence to First line ART or who are suspected of
treatment failure, or who will start Second line ART, the objectives of adherence counseling
are:
To improve the adherence to medications so that ART is successful
To encourage self management of medications
To foster honest communication between provider and patient
To respect patient choices and decision-making related to their HIV related
medical care
Patients dont want to disappoint their health care provider. The challenge is: how
do you make it okay to say no to doctors/counselors/nurses; or make it okay to
say I cant do this
Section II: OPERATIONAL GUIDELINES
2.1 STATE AIDS CLINICAL EXPERT PANEL (SACEP)
a. State AIDS Clinical Expert Panels (SACEP) have been constituted at all COEs and
ART plus centre to review the patients referred to them with need for alternative
First line and Second line ART. Each COE/ART plus centre has ART centres linked
to it and patient from these centers only will be reviewed by a particular COE/ART
plus centre.
b. The SACEP will review the patient and his/her records and will approve the COE/
ART plus to provide PI based Alternate First line drugs if the patient is found
to have severe toxicities to the First line ART or Second line ART as per clinical
protocols.
c. Once the decision is made by SACEP to provide alternative First line ART to the
patient reviewed, patients who are recommended for PI based alternate First line
are transferred out to the CoE/ART plus centre from the referring centre.
d. The patient shall be started alternative First/Second line ART only after adherence
counseling has been done and patient has been assessed to be prepared for 100%
adherence to the regimen.
e. Patients who have not been found eligible for Second line ART after
SACEP review a detailed follow up plan should be given to the referring
ART centre in the reply back form.
State AIDS Clinical Expert Panel (SACEP) have been established at each centre of
excellence/pCoE/ART plus centre. It consists of:
1. P
rogram Director/Deputy Program Director of COE/pCoE, Nodal Officer of
ART plus centre
2. O
ne more ART expert (preferably not from the same ART centre) - Panel to
be formed by NACO
3. Regional Coordinator/Joint Director (CST)/Consultant (CST) at SACS/DPM.
In addition to the above, there would be observers from central level regularly for
monitoring purposes.
The Terms of reference of SACEP/are:
Review and decide on all cases referred by the referring ART centre for PI based alternate
First line/Second-line ART provision both for eligibility for Viral load testing and starting
Second line or alternative First-line ART regimen
Meet at the COE/ART plus centre to review cases every Tuesday (or a prefixed day) (next
working day in case of a holiday). This is to ensure that there is no delay in review and
processing of the case referred for review of suspected treatment failure. A maximum
of 15-20 patients shall be reviewed at each meeting (old and new). However if there
are too few patients, the meeting may be deferred to the next week. If the number
of patients on next week is again too small, the meeting still should be held to avoid
delay. It should be ensured that there is minimum time taken for review of patients
and provision of drugs. All efforts should be made to ensure that this period does not
exceed four weeks.
Mentoring and ensure high quality case management of the PLHA on Second-line ART
by the referring ART centre
Document the registration and monitor progress of all patients suspected of treatment
failure sent for SACEP/review
The SACEP will follow the technical protocols as laid out by NACO in section I of these
guidelines.
However for all technical issues, the ART plus centres can refer difficult cases to SACEP of their
CoE in their region. For patients requiring any further technical/operational clarification,
COE/ART plus centres can refer cases to NACEP (National AIDS Clinical Expert Panel) at
Secondline2008@gmail.com and drbbrewari@yahoo.com. The functioning of NACEP will
be coordinated by Dr B B Rewari, NPO (ART). This panel can have representatives from
TRG, institutions or independent experts that would be deemed most appropriate for the
query under consideration. Hence, the composition of the NACEP will be dynamic and its
composition will vary depending on the type of technical query. This will ensure that most
appropriate response and guidance is provided for the query by the variety of experts and
expertise on various areas under treatment and care for HIV.
Referral to SACEP
Once a patient on ART is suspected to have toxicity to any ARV or is suspected to have
treatment failure, the ART centre SMO/MO should follow the steps mentioned below:
Step 1 The referring ART centre should go through section on Suspecting drug
toxicities among patients on First line therapy/Suspected treatment failure
(Protocol A1.1).
Go through the toxicities grading in ART guidelines.
Referring ART center will send photocopies of patients records and photo
documentation for type of toxicities to SACEP coordinator at CoE/ART plus
centre together with Referral/Reply Form (Annex II) and confirm that SACEP
coordinator has received it.
Step 2 SACEP coordinator/COE research associate will First enter the patient details in
the SACEP register and then get the patients history reviewed and if eligible give
appointment date/time (2 alternative dates) to the referring centre by e-mail.
Before giving appointment the CoE/ART plus centre may request for any other
patient treatment related documents.
Step 3 The referring ART center will then communicate the date/time to patient by
phone/personal contact by ORW
Step 4 Only after the SACEP has reviewed the patient and recommended initiation of
Second line/Alternate First line ART (PI based), in its reply form, will the patient
be transferred out to the CoE/ART plus centre.
Note:
For alternate First line ART: only those patients would be transferred out to CoE/
ART plus centre who are being initiated on PI based alternate First line ART. For
other patients for whom substitution is being done with in NNRTI or NRTI class of
drugs no transfer out is required and treatment can be changed at that ART centre
itself after SACEP recommendations. SACEP review is not required for TDF based
regimen. However e SACEP approval shall be required for d4T based regimen as only
limited quantities of d4T shall be procured in future
For Second line ART: all patients starting Second line ART need to be transferred
out to CoE/ART plus centres.
2.2
E LIGIBILITY AND CRITERIA FOR PROVISION OF SECOND LINE ART
All patients who require Second line ART shall be reviewed by SACEP as per laid
down referral procedure, irrespective of the fact whether they started treatment
in private sector or NACO centres
The SACEP review will be based on the referral from the ART centre providing First
line ART to the patient suspected of treatment failure. Each COE/ART Plus Centre
will have defined ART centres linked to it and patients from these centres only will
be reviewed by a particular COE/ART Plus Centre.
Criteria for provision of Second line ART:

Referred by the NACO ART centre following the NACO protocol on determining
treatment failure (section 1.6)
Reviewed by the SACEP and determined to be medically eligible as per the NACO
protocol for Second line provision
Has been assessed by counselor/nurse/doctor for adherence and is prepared for
Second line treatment
Should have family support/treatment supporter, and linked to NGO/CBO/CSC/ICTC
for outreach/community/home based care services and monitoring of adherence
Furthermore, the patient to be provided Second line ART shall need to sign a consent
form for informed consent (ANNEX III) for home visits/followed at the community by link
worker/NGO/positive network/ICTC which will support the adherence at community level
for Second line provision.
The SACEP coordinator at COE/Data Manager at ART Plus Centre shall coordinate the
meeting of the SACEP to be held at the COE/ART Plus Centre meeting room. The COE/ART
Plus Centre will request the patient to be physically present for the review panel. The SMO
at ART centre should also be involved in the meeting.
2.3 PROTOCOL FOR SACEP REVIEW
Follow Protocol A1.1 for Suspected treatment failure and then e-mail the details (brief
ART
Step 1
history, clinical stage and serial CD4 values, reasons for referrals) of patient to CoE/pCoE/
ART plus centre to get appointment dates
CoE SACEP coordinator/ART plus centres data manager will enter patient details into
SACEP register (1 SL+AL) CoE SACEP coordinator/CoE research associate/ART plus centres
Step 2
data manager will review patient history details sent by centre and give appointment date
(two alternatives) and time to the referring centre by e-mail for review by SACEP
The referring ART centre will then communicate the date/time to patient by phone and
Step 3
personal contact by ORW/DLN volunteer
Referring ART centre will send photocopies of patient records together with Referral/Reply
Step 4 Form VI and confirm that CoE SACEP coordinator/ART plus centres data manager has
received it. CoE SACEP coordinator/ART plus centres data manager prepares weekly SACEP
meeting formats (2 SL)
Step 5 The SACEP will review the case notes only in the presence of the patient and guardian
The SACEP will order a Viral load test according to Protocol A 1.2.
Step 6 Blood sample to be taken to the linked Viral Load Lab will be processed according to
Laboratory guidelines section
The SACEP will review the Viral load results in next meeting and decide on management of
the patients and will document one of the following decisions:
Step 7 Provide Second line ART
Not eligible for Second line ART
Re-evaluate/others
Once the decision is made by the SACEP to provide Second line ART to the patient
reviewed, the clinical management of the patient will be done at the CoE/pCoE/ART plus
Step 8
centre itself. Only the Program Director or Deputy Program Director of CoE/pCoE and/or
Nodal officer of ART plus centre prescribe Second line ART
The CoE SACEP coordinator/ART plus centres data manager shall inform the referring ART
centre for the following actions:
Step 9
Transfer-out the patient in the M&E formats, to CoE/pCoE/ART plus centre,
Send the completed reply form to the referring ART centre
The patient must undergo 3 counseling sessions (minimum) to ensure treatment
Step 10
preparedness at the CoE/pCoE/ART plus centre
Step 11 The follow up visits shall be monthly at the CoE/pCoE/ART plus centre
After 6-months of Second line ART, the follow up Viral load test has to be performed. The
result will be reviewed by CoE/pCoE/ART plus centre. The patients who have suppressed
Step 12
viral loads with clinical stability may be transferred back to the referring ART centre, after
ascertaining patents willingness
CoE SACEP coordinator/pCoE/ART plus centres data manager to send SACEP Monthly
Step 13 report to NACO by e-mail by 4th of every month (Secondline2008@gmail.com) under over
all supervision of Program Director/Deputy Program Director &/or Nodal officer
The COE Program Director/Deputy Program Director &/or Nodal officer of ART Plus Centre
will be the physician responsible; backed up by the COE/ART Plus ART centre staff to ensure
high quality of care for the patient on 2nd line ART. Prescription of the 2nd line ART shall be
done only by the Program Director or Deputy Program Director of CoE/pCoE and/or Nodal
officer of ART plus centre.
The patient who is confirmed treatment failure and is to be started 2nd line may be admitted
at the COE for treatment of any OI or for reinforcing adherence, if required. The COE ART
team shall ensure that the patient on 2nd line is linked to a NGO/CBO/ICTC/CSC for care and
support as well as the positive network for other support. Condom use, nutrition advice
and positive prevention are to be emphasized.
Details in the reporting and recording formats should be completed by the COE staff so that
good documentation is present.
2.4 TOR OF ADDITIONAL MANPOWER: SACEP COORDINATOR
For carrying out these activities, each COE shall be provided with an additional manpower
in form of a SACEP coordinator. The TORs for SACEP Coordinator are:
1. Screen and review all records and communications of the referrals made to the SACEP
2. Maintaining SACEP-schedule diary, schedule and communicate appointment dates

of patients to the referring centres
3. Organize SACEP meetings and coordinate with members of the SACEP
4. Ensure laboratory test results of patients attending are available for SACEP meetings
5. Coordinate with pharmacist for patient drug transfers
6. Ensure follow-up of patients attending SACEP
7. Be responsible for patients registration, maintaining all forms and registers related
to SACEP
8. Prepare and send SACEP reports to SACS and NACO.
9. Coordinated activities of in the region linked to the CoE
10. Be responsible for receiving and sending communications from and to the linked
ART Centres
11. Be responsible for all data entries, maintaining and updating all records, registers
and files pertaining to the CoE
12. Assist the Program Director and the Deputy Program Director of CoE in receiving
and sending all communications related to the CoE
13. Work in the ART centre and perform the duties of Data Manager, if and when
required.
14. Responsible for procurements, maintaining accounts, audits, handling contingency
petty cash of the CoE
15. Assist the training and mentoring coordinator in communications and maintaining
records
16. Perform any other job as assigned by the Program Director/Deputy Program Director
of the CoE.
For SACEP meetings at the ART plus centres, the coordinator shall be one of the data
managers at the centre and no additional staff shall be provided presently.
Section III: M & E TOOLS
The soft copies of revised M&E tools have been sent to all COE and ART plus
centres with instructions on how to use them and only those are to be used. The
formats are enclosed at Annex IX.
The monitoring plan for Second-line ART focuses on two main aspects of National
ART Programme namely Clinical Monitoring of the Patients and Programme
Performance. The system developed; tries to build on the existing monitoring systems
existing at ART centres. Refinements are added in current tools to record details of
Second line and additional tools are developed for critical areas of monitoring.
These tools would allow:
Clinicians to effectively monitor the patient on 2nd line clinically, and
The ART programme to monitor the progress in implementation, identify

problems, refine and adapt the implementation strategies; assess the
effectiveness of the interventions.
3.1 INSTRUCTIONS FOR MONITORING/RECORDS KEEPING FOR SECOND

LINE ART
1. When the patient is referred from any ART centre to COE for evaluation, the
patient is NOT Transferred Out and would continue to receive the First line
drugs from referring ART Centre till recommended otherwise. SACEP/COE (/ART
Plus Centre) will inform the referring centre once decision is made if patient is to
be transferred out or not.
2. The patient once recommended for 2nd line; is then transferred out (T/O) to CoE/
ART plus centre. The normal procedure of T/O is followed. The records are thus
transferred as per the usual procedure, if not already done.
3. At the ART centre of COE/ART Plus centres, the current ART enrollment register is
used for recording the clinical details of the patient on Second-line by filling the
information on switch
4. In the same ART enrolment register a post fix to the ART registration S (Second
line) can be indicated in the First blank column before ART date of start and A
for alternative First line and registration number are given in a sequential order in
continuation to the patients on First line ART.
The summary of Second line and alternative First line formats is as below:
Monitoring and Evaluation tools for Second line and Alternative First line ART
(Adults and Children)
(To be maintained at CoE/pCoE/ART plus centres)
Tool/Abbreviations M & E Tool- formats/Registers Directions

To be generated at ART Centre when
referring the patient. The reply portion
SACEP Referral and Reply
RRF to be sent back to referring centre
form
by SACEP after the evaluation of the
patient. (computer printed form only)
To be maintained at CoE/pCoE/ART
1 plus Centre by SACEP coordinator/
data manager (Hard bound printed
SACEP register (for all patients register to be supplied by the SACS).
1 SL*+ AL**
being referred to SACEP ) There should be no more than six
rows per page in order to ensure that
there is adequate space for writing
the details.
SACEP Meeting format
(alternative First line) This
To be prepared before every SACEP
format should be prepared
meeting; given to all members dur-
before every SACEP meeting for
2 AL ing the meeting; and maintained at
all patients (children and adults)
all CoE/pCoE/ART plus centres (in
to be reviewed in that particular
file ring binder and soft copy)
meeting for consultation for
Alternative First line ART
2 SACEP Meeting format (Sec-
ond line)
To be prepared before every SACEP
This format should be prepared meeting, given to all members dur-
2 SL before every SACEP meeting ing the meeting and maintained at
for all patients (children and all CoE/pCoE/ART plus centres (in
adults) to be reviewed in file ring binder and soft copy)
that particular meeting for
suspected treatment failure.
Monthly reporting format
(Second line and alternative
First line) To be submitted to NACO by
3 3 AL+ SL Combined monthly reporting email by 4th of every month at
format for Second line and Secondline2008@gmail.com.
alternative First line ART for
adults and children
Tools to be maintained at all CoE/pCoE/ART plus centres (in ring binder file and/or
soft copy):
Line list (alternative First
line) To be maintained at all CoE/pCoE/
4 AL Cumulative list of patients ART plus Centres in one continuous
ever initiated on alternative excel sheet (soft copy only)
First line ART
4
To be maintained at all CoE/pCoE/
Line list (Second line) ART plus centres in one continuous
Cumulative list of patients excel sheet (soft copy only). To be
4 SL
ever initiated on Second line maintained at referring ART centre
ART also after transfer back of the pa-
tient after 6 months.
Linked Centre wise cumulative
Centre wise (linked centre
information about PLHIV. To be
information) break up for PL-
5 5 SL maintained at all CoE/pCoE/ART
HIV initiated on Second line
plus centres in one continuous
ART
excel sheet (soft copy only)
To be obtained from each patient
by SACEP coordinator/data man-
Consent form for Second line
6 CF ager when starting Second line ART
ART
(computer print out, signed form to
be kept in ring binder form)
Note: Out of this only SACEP register is to be printed as hard bound register as per printing instructions
sent to SACS. Rest are to be used as soft copies and print out of soft copies to be kept at CoE/pCoE/ART plus
centres in separate ring binder files year-wise.
* SL- Second line ART
**AL- Alternative First line ART
All Second line treatment related formats are enclosed at Annexure IX.
1. SACEP Register (1 SL + AL) would be maintained by all CoE and ART Plus centers that
conduct SACEP meetings. The SACEP register is a clinic administration tool which
helps to track patients from referral to outcomes, provide information for weekly and
monthly reporting to NACO.
The SACEP coordinator (COE)/data manager (ART Plus Centre) is responsible for
maintaining and updating the register
To fill in the register, please note that:
o It has to be printed in the form of a register and all patients who are referred to
CoE/ART plus centre for SACEP; should be entered in this register
o Patient is to be entered only ONCE in SACEP/register with details in same row.
No multiple entries for same patient should exist (unique) but if the patient was
not found eligible for review or after review it was decided by the SACEP that it
is a wrong referral then a new SACEP number would be given the next time the
patient is referred to SACEP.
2. SACEP Meeting format (2 SL & 2 AL) records the details of every meeting and is to be
maintained at COE/ART plus centre
3. Second line monthly ART centre report (3SL + AL) - this report is to be sent on a monthly
basis to NACO by all CoEs and ART plus centres. This report should be generated after
compilation of line lists from all the linked ART centres.
All COE/ART plus centre will sent monthly report for alternative First line and Second
line combined formats for adults and children to NACO at Secondline2008@gmail.com
latest by 4th of every month in prescribed format.
4. Line Lists (4SL/4 AL): All ART centres should maintain a list of patients on Second line
and Alternative First line ART in prescribed format and send it to their linked CoE/ART
plus centre, so that Second line monthly ART centre report can be generated.
5. Centre wise information (5SL) - linked centre wise detailed information on patients on
Second line should be available with all CoEs and ART plus centres.
Note: Electronic copies (excel) are available for the above formats from NACO. Contact
Secondline2008@gmail.com
DATA FLOW
ART center refers patients to SACEP (email).

Do not stop First line ART
SACEP Referral form (ANNEX II)

Informs appointment time (email)
& photocopy of relevant documents (courier)
SACEP coordinator:
Vets referrals & ensure documents/tests ready
Inform ART center appointment date for SACEP
Enters patient details into SACEP register (SL-1)
Reply form,
(ANNEX II)
SACEP meeting:
Weekly SACEP meeting sheets (SL-2)
Update details/decision in SACEP register (SL-1)
Lab request form (ANNEX VII)
Patient sent for VL tests
Patient not eligible

for 2nd line ART Patient for re-evaluation
SACEP reviews VL results
& decides treatment plan Send patient back to original ART center with
written treatment plan and SACEP advice
Patient eligible
for 2nd line ART:
Returns for 2nd
Line ART initiation
Refer back to
COE/ART Plus Centre original ART center,
VL<400 with treatment plan
(1) Informs ART center to transfer 2nd line ART
out patient initiated and Transfer-Out
continued for 6 month
(2) Entry into COE/ART Plus Centre Pre
6 months at VL and CD4 If no OI send the
ART and ART enrollment register as
COE/ART Plus patient back to
transfer in;
Centre the referring ART
(3)Counsel treatment preparedness & VL>400 centre or else
use counselling diary retain the patient
and repeat viral
load at another
6 months
Section IV: LABORATORY GUIDELINES
4.1 INTRODUCTION:
HIV infection has become a pandemic in the last 20 years. The dynamics of the HIV/
AIDS epidemic in India will have a major impact on the overall disease burden of HIV
in the Asia-Pacific region and the world. National estimates indicate that India has
2.1 to 2.09 million people living with HIV infection (2011). The overall average adult
prevalence in India is 0.27%.
The viral load assay (estimation of copies of HIV-1 ribonucleic acid (RNA) in plasma of
infected individuals) is critical in monitoring patients response to ART (Antiretroviral
therapy) and progression towards AIDS. Hence, HIV-1 viral load assay would be one
of the key parameters for assessment of patients with suspected treatment failure on
First line ART (who may be requiring Second line ART). HIV-1 viral load assay results
will help to initiate Second line ART at designated centers as per NACO guidelines.
Viral load assays quantify the amount of HIV-1 RNA circulating in the blood of an
infected individual. Although total quantification includes cell-free virus, virus in
infected cells in all compartments of the body as well as integrated provirus, the
easiest measurement of viral load is of cell-free virus in an individuals plasma.
Currently there is no clinical indication for viral load testing of tissues. HIV-1 plasma
viral load (PVL) level is being successfully used to predict time to progression to AIDS
and to assess efficacy of ART. During treatment, the decay of viral load in tissues
typically corresponds with virologic responses in plasma, making blood plasma a
useful sentinel for virologic response in general.
4.2 INTENDED USE OF HIV-1 PVL ASSAY IN NACOS SECOND LINE ART
INITIATIVE:
The HIV-1 PVL assay will be performed in HIV infected individuals that fail First line
ART at NACO designated ART sites. The results of PVL assay will be used to decide the
initiation of Second line ART.
The PVL assay will be performed:
Before starting Second line ART to get the reference value to decide on further
course of action. A PVL measurement will be performed on patients referred by
SACEP. The decision on whether to switch ART or not will be made based on the
viral load detected as detailed below:
- PVL < 400copies/ml: No change in 1st line ART
- PVL 400-5,000 copies /ml: Repeat PVL after 3 months with stringent monitoring of
patient for adherence to First line ART regimen
- PVL >5000 copies/ml: Start patient on Second line ART. Repeat PVL after 6 months to
assess suppression in viral load
- Repeat PVL assay at 12 months if 6 months PVL is more than 400
Repeat PVL on the same patient must be done at the same laboratory with the same
technique/procedure, using the same platform
* This must be especially noted for laboratories which are initially linked to other
laboratories and likely to have their own viral load assay set ups in the near future
If treatment failure is suspected based on immunological (Second confirmation of CD4
T cell levels) and/or clinical criteria, the ART centre must follow the NACO protocol for
management as detailed in pages 19 (protocol A1.1).
The ART centre will suspect treatment failure in patients who are on First line ART for at
least 6 months and have:
A new OI (clinical failure)
Slow rise of CD4 cells or failure of CD4 cells to rise after 6 -12 months of treatment
Decline in CD4 cells by 50% after an initial rise, as per NACO/WHO guidelines
Perform CD4 cell estimation immediately in cases of suspected clinical failure and repeat
after 4 weeks for confirmation of failure as per protocol A1.1
Simultaneously undertake the following:
o Evaluate patient for ART adherence

o Rule out presence of OIs like tuberculosis, oesophageal candidiasis, etc.
o Ensure patient has been on cotrimoxazole prophylaxis.
o Treat and review OIs if present.
o The ART centre to send the request form with complete patient details along
with the confirmed contact phone number to the nodal officer.
The nodal officer refers such a patient to State AIDS Clinical Expert Panel (SACEP) at COEs
and/or ART plus Centres for decision on HIV-1 viral load testing.
Eligibility
All HIV positive patients showing signs of failure on First line ART will be eligible for review
by SACEP following the proper referral procedures from the ART centres:
State-wise list of CoEs and ART plus centres
State COE*/ART Plus centre

Tamilnadu Government General Chest Hospital (GGCH), Tambaram*
Government Mohan Kumaramangalam Medical College, Salem
Madurai Medical College, Madurai
Tirunelveli Medical College, Tirunelveli
Maharashtra Grant Govt. Medical college and Sir JJ Hospital, Mumbai*
Govt. Medical College, Aurangabad
Government Medical College, Sangli, Maharashtra
B. J. Medical College & Sassoon Hospital, Pune
Govt. Medical College, Nagpur
Gujarat B. J. Medical College (BJMC), Ahmadabad*
Govt. Medical College, Majura Gate, Surat
Pandit Din dayalUpadhyay Hospital, Rajkot
Karnataka Bowring and Lady Curzon Hospital, Bangalore*
Karnataka Institute of Medical Sciences, Hubli, Karnataka
VijayanagaraInstitute of Medical Sciences, Bellary, Karnataka
District Hospital, Gulbarga, Karnataka
District Hospital, Udupi, Karnataka
Andhra Pradesh Gandhi Hospital and Medical College, Hyderabad*
Government General Hospital, Vijayawada, Andhra Pradesh
Rajiv Gandhi Institute of Medical Sciences, Kadappa, Andhra Pradesh
King George Hospital, Visakhapatnam, Andhra Pradesh
West Bengal School of Tropical Medicine (STM), Kolkata*
New Delhi Maulana Azad Medical College (MAMC), New Delhi*
Kerala Govt. Medical College, Trichur
Assam Medical College and Hospital, Guwahati
Manipur Regional Institute of Medical Sciences (RIMS), Imphal*
Bihar RajendraMemorial Research Institute of Medical Sciences, Patna
Madhya Pradesh Gandhi Medical College, Bhopal, Madhya Pradesh
Rajesthan SawaiManSingh Medical College and Hospital, Jaipur
Uttar Pradesh King George Medical College, Lucknow
Mizoram Civil Hospital, Aizwa
Punjab Government Medical College, Amritsar
Panjab/Haryana Post Graduate Institute of Medical Education and Research (PGI), Chandigarh*
Uttar Pradesh Institute of Medical Sciences (BHU), Varanasi*
Uttaranchal Doon Hospital, Dehradun
Jammu & Kashmir Government Medical College, Jammu
Orissa Shrirama Chandra BhanjMedical College, Cuttack
13 more ART plus centres have been sanctioned so as to have at least one ART plus centre
in each state to provide Second line ART
NOTE: Blood is not to be drawn for a viral load test within four weeks of any infection or
immunization.
Protocol for the review panel
The SACEP will review the case notes along with the patient.
The panel will then order a viral load test if required. Specimens (whole blood and DBS) will
be collected from the patient at the COE on a designated day and sent to the identified viral
load lab as detailed below in the section on specimen collection, storage and transport. The
SACEP will meet on the following designated day (which if happens to be a holiday then on
the next working day) to review the results of viral load assay and, based on the result of
PVL, decide on further management of the case.
4.3 TECHNIQUES OF HIV 1 PVL ASSAY:
Viral load assays measure the amount of HIV-1 RNA in the collected plasma specimen. HIV-1
RNA is responsible for HIV replication. The amount of HIV-1 RNA in plasma can be measured
by the following different techniques for measurement of HIV-1 RNA.
Quantitative PCR (polymerase chain reaction) is the most frequently used test.
For PCR the viral RNA is extracted; an enzyme converts the extracted RNA to DNA
(cDNA); this DNA is then multiplied many folds by the help of an enzyme polymerase;
the product is detected through changes in the intensity/color of certain chemical
markers. This process makes the detection of viral RNA easier. The original number of
RNA copies would be then quantified based on the final numbers of cDNA obtained.
Test results are reported as HIV-1 RNA copies/ml.
The bDNA (branched DNA) is a fairly frequently used test. It makes use of signal
amplification (light emitting material). This material binds with the HIV particles.
The amount of light is measured and converted to a viral count.
NASBA (Nucleic Acid Sequence Based Amplification Assay) is an in vitro nucleic

acid amplification test for quantification of amplified HIV-1 RNA which is measured
by means of electrochemiluminescence.
The PCR test results are often different from the bDNA results for the same specimen. Because
the tests are different, only one kind of test (PCR or bDNA) should be used to measure a
persons viral load over time.
Viral load assay results are reported as copies of HIV-1 RNA in one milliliter of blood. The best
viral load assay result in patients on ART is undetectable viral load. This does not mean
that there is no virus in the blood; it just means that the level is not enough to be detected
through the test used. Undetectable level (No of copies/ml of plasma) will depend on the
sensitivity of the assay system used.
Some relevant terminologies
Sensitivity: Sensitivity is defined as the lowest viral load level that can be detected in
the specimen 95 percent of the time. The statistical method of assessing sensitivity
is generally considered to be the standard to determine the quantitative limit of
detection (LoD) for quantitative HIV-1 RNA assays
Precision: The precision or reproducibility of an assay is defined by its ability to

obtain the same value when tested repeatedly. In viral loads, precision is measured
by the ability to detect fold changes in the levels of the viral loads.
Dynamic Range: The dynamic range of an assay is defined as the quantitative range
over which the results are reliably reported.
4.4 PLASMA VIRAL LOAD ASSAYS CURRENTLY IN USE IN NACOS SECOND-LINE ROLL OUT:
4.4.1 AMPLICOR HIV-1 MONITOR TEST, VERSION 1.5
The Amplicor HIV-1 Monitor Test, version 1.5 (v1.5) is an in vitro nucleic acid amplification
test for the quantification of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in human
plasma. The Amplicor HIV-1 Test, version 1.5 uses PCR technology to achieve maximum
sensitivity and dynamic range for the quantitative detection of HIV-1 RNA in EDTA anti-
coagulated plasma.
The Amplicor HIV-1 Monitor version 1.5 (v1.5) is programmed on, and approved for use on
Applied Biosystems Gene-Amp PCR system 9600/9700 thermal cycler. In Amplicor HIV-1
monitor the specimen preparation is manual, the amplification is automated on the ABI
9600/9700 and detection is by manual ELISA or automated ELISA reader.
The test can quantitate HIV-1 RNA over the range of 50-750,000 copies /ml by using a
combination of two specimen preparation procedures, the Standard (dynamic range
400-750,000 copies /ml) and Ultra Sensitive (dynamic range 50-1,00,000 copies/ml)
procedures. Test results less than 400 are below the lower limit of detection of the Standard
test. If quantitative results are desired for such specimens, original plasma specimens
should be retested using the Ultra sensitive specimen preparation procedure
This test is based on five major processes: specimen preparation, reverse transcription
of target RNA to generate complementary DNA (cDNA); PCR amplification of target cDNA
using HIV-1 specific complementary primers; hybridization of the amplified products to
oligonucleotide probes specific to the target(s); and detection of the probe bound amplified
products by colorimetric determination.
The Amplicor HIV-1 Monitor Test, v1.5 can be used with either of two specimen preparation
procedures, the Standard procedure or the Ultra Sensitive procedure. In the Standard
specimen preparation procedure, HIV-1 RNA is isolated directly from plasma by lysis of
virus particles with a chaotropic agent followed by precipitation of the RNA with alcohol.
With the Ultra Sensitive specimen preparation procedure, HIV-1 viral particles in plasma
are concentrated by high speed centrifugation, followed by lysis of the virus particles with
a chaotropic agent and precipitation of the HIV-1 RNA with alcohol. A known number of
quantitation standard RNA molecules are introduced into each specimen with the lysis
reagent. The HIV-1 Quantitation Standard is carried through the specimen preparation,
reverse transcription, amplification and detection steps and is used for the quantitation of
HIV-1 RNA in the test specimen.
4.4.2 COBASAMPLICOR HIV-1 MONITOR TM TEST, VERSION 1.5
The CobasAmplicor HIV-1 Monitor Test, version 1.5 (v1.5) is an in vitro nucleic acid
amplification test for the quantitation of Human Immunodeficiency Virus Type 1 (HIV-1)
RNA in human plasma on the CobasAmplicorTM analyzer.
In CobasAmplicor the specimen preparation is manual and the amplification and detection
steps are automated.
The test can quantitate HIV-1 RNA over the range of 50-750,000 copies/mL by using a
combination of two specimen preparation procedures, the Standard (dynamic range 400-
750,000 copies/ml) and Ultra Sensitive (dynamic range 50-100,000 copies/ml) procedures.
Test results less than 400 are below the lower limit of detection of the Standard test. If
quantitative results are desired for such specimens, original plasma specimens should be
retested using the Ultra sensitive specimen preparation procedure.
This test is based on five major processes: specimen preparation; reverse transcription
of target RNA to generate complementary DNA (cDNA); PCR amplification of target cDNA
using HIV-1 specific complementary primers; hybridization of the amplified products to
oligonucleotide probes specific to the target(s); and detection of the probe bound amplified
products by colorimetric determination.
The CobasAmplicor HIV-1 Monitor Test, v1.5 can be used with either of two specimen
preparation procedures, the Standard procedure or the Ultra Sensitive procedure. In the
Standard specimen preparation procedure, HIV-1 RNA is isolated directly from plasma by
lysis of virus particles with a chaotropic agent followed by precipitation of the RNA with
alcohol. With the Ultra Sensitive specimen preparation procedure, HIV-1 viral particles in
plasma are concentrated by high speed centrifugation, followed by lysis of the virus particles
with a chaotropic agent and precipitation of the HIV-1 RNA with alcohol. A known number
of quantitation standard RNA molecules are introduced into each specimen with the lysis
reagent. The HIV-1 Quantitation Standard is carried through the specimen preparation,
reverse transcription, amplification and detection steps and is used for the quantitation of
HIV-1 RNA in the test specimen.
4.4.3 COBAS TAQMAN HIV-1 TEST
The COBAS TaqMan HIV-1 Test is an in vitro nucleic acid amplification test for the quantitation
of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in human plasma with EDTA, using
the High Pure System Viral Nucleic Acid Kit for manual specimen preparation and the COBAS
TaqMan analyzer for automated amplification and detection. The test can quantitate HIV-1
RNA over the range of 47 - 10,000,000 copies/ml
The COBAS TaqMan HIV-1 Test utilizes real time PCR technology to achieve maximum
sensitivity and dynamic range for the quantitative detection of HIV-1 RNA in EDTA anti-
coagulated plasma. The use of dual-labeled fluorescent probes provides for real-time
detection of PCR product accumulation by monitoring of the emission intensity of
fluorescent reporter dyes released during the amplification process. The COBAS TaqMan
HIV-1 Test accurately provides quantitative results over a very wide dynamic range since the
monitoring of amplicon is performed during the exponential phase of amplification. The
higher the HIV-1 titer of a specimen, the earlier the fluorescence of the reporter dye of the
HIV-1 probe rises above the baseline fluorescence level.
The COBAS TaqMan HIV-1 Test is based on four processes: Specimen preparation
to obtain HIV-1 RNA; Automated reverse transcription of the target RNA to generate
complementary DNA (cDNA); Simultaneous PCR amplification of target cDNA using HIV-1
specific complementary primers; and detection of cleaved dual fluorescent dye-labeled
oligonucleotide detection probes.
The COBAS TaqMan HIV-1 Test processes EDTA containing plasma specimens and isolates
HIV-1 RNA through a generic manual specimen preparation (in case ampliprep is not
available) based on nucleic acid binding to glass fibers. The HIV-1 virus particles are lysed by
incubation at an elevated temperature with a protease and chaotropic lysis/binding buffer
that releases nucleic acids and protects the released HIV-1 RNA from RNAs in plasma. A
known number of HIV-1 Quantitation Standard Armored RNA molecules are introduced
into each specimen along with the lysis reagent. Subsequently, isopropanol is added to
the lysis mixture which is then centrifuged through a column with a glass fiber insert.
During centrifugation, the HIV-1 RNA and HIV-1 Quantitation Standard RNA are bound to
the surface of the glass fiber filter. Unbound substances, such as salts, proteins and other
cellular impurities, are removed by centrifugation. The adsorbed nucleic acids are washed
and eluted with an aqueous solution. The disposables allow for a parallel processing of 12
specimens or multiples thereof. The processed specimen, containing HIV-1 RNA and HIV-1
Quantitation Standard RNA, is added to the amplification/detection mixture. The HIV-1 target
RNA and the HIV-1 Quantitation Standard RNA are then reverse transcribed, amplified and
detected on the COBAS TaqMan - analyzer using the amplification and detection reagents
provided in the test kit.
4.5 SPECIMEN COLLECTION, STORAGE, AND TRANSPORTATION:
4.5.1 COLLECTION DAYS AND TIMINGS
Specimen collection is to be done between 11.00 A.M to 1:00 PM on SACEP day as

decided by the centre.
In case the specimen collection day is a holiday, specimen collection is to be posted on
an alternate day with prior arrangement with the receiving laboratory.
Do not collect specimen if next day to SACEP is a holiday (as specimens have to be
processed for HIV-1 PVL by the receiving laboratory within 24 hours of collection)
Previous arrangement with testing centre to be made in case the specimen is to be collected
on a day not scheduled for the purpose (Collection and transport of specimen)
4.5.2 SPECIMEN COLLECTION
Standard work precautions are to be followed stringently
Page 1 of the VL-1 form (as per Annex VII) is to be filled mandatorily in duplicate/
photocopy. (Specimens accompanied with incomplete forms will be rejected)
Confirm information on VL-1 form (patients name, registration/accession number, test

needed, date and time of collection, and physicians/clinics name, etc) mandatorily
before collection of specimens
Sterile EDTA (lavender top) evacuated blood collection tubes are to be used.
The blood collection tubes are to be labeled (cryolabel) with patients name, registration/
accession number, test needed, date and time of collection, and physicians/clinics
name. The information on the form should match the information on the specimen
collection tube
4ml blood is to be collected and placed in prescribed sterile tubes using EDTA
(lavender top) as the anticoagulant. Do not collect blood in heparin vials. (The choice
of anticoagulant used in blood collection tubes can significantly alter viral load results,
by affecting either the virion decay rate ex vivo or the detection by the assay type used.
Plasma treated with sodium heparin is not appropriate for PCR assays because heparin
is a potent inhibitor of PCR)
In case the linked HIV-1 PVL laboratory is in a different city, Dried Blood Spot (DBS)
Preparation and Storage (as per Section 4.13) and then plasma separation (as per below)
are to be performed by the ART Centre itself.
In case the linked laboratory is in the same city or same hospital, DBS Preparation
and Storage (as per Section 4.13) and then plasma separation (as per below) are to be
performed by the PVL laboratory within 6 hours of receipt of specimen.
4.5.3 PACKAGING AND TRANSPORTATION
All specimens will be transported by hand by lab technicians of the centre of

excellence
The specimen is to be packaged carefully to protect from breakage, and leakage and
insulated to protect from extreme temperature. Cool packs are to be used to maintain
temperature of 2-80C. Ensure whole blood does not freeze during transportation.
For packaging, the tube containing the specimen is placed in a leak proof container (e.g.
a sealed plastic bag).
The cool packs are to be placed around and the package is to be placed inside a puncture
proof container with sufficient material to absorb all the contents in case the tube
breaks or leaks.
Cap the container tightly.
Place the VL-1 form in an envelope and fasten securely to the outside of the container.
A biohazard label should be pasted on the visible outer surface of the package containing
the specimens.
In case the laboratory is located in the same city: The Lab technician of the ART centre
should transport the specimen with the VL-1 form in duplicate and ensure delivery to
the testing lab of the whole blood specimen at 2-8oC within 3 hours of collection (i.e. by
2.00 P.M. on Monday/Tuesday afternoon).
In case the laboratory is located in a different the city: The Lab technician of the ART
centre should transport the plasma specimen (First having prepared, packaged and
stored DBS; and then separated the plasma at the ART centre) with the VL-1 form in
duplicate and ensure delivery to the testing lab of the plasma specimen at 2-8oC within
24 hours after collection (i.e. by 10AM. on Tuesday/Wednesday).
The technician from the centre of excellence carrying the specimens must participate
with the technicians at the PVL laboratory in the processes of estimation of HIV-1 PVL in
order to learn the techniques involved.
The DBS samples will be collected and stored as per section 4.13. It is recommended that
the DBS samples be stored at 2-8oC for 20 days and then be couriered to NARI, Pune along
with the consent forms. It is important to note that the consent form must be sent to the
lab making DBS in case of intercity linkages for sending to NARI, Pune. The details on the
envelope may be as follows:
For Second Line roll out

Dr R Paranjape
National AIDS Research Institute (NARI)
73 G Block, MIDC
Bhosari, Pune-411026
Maharashtra, India
4.5.4 RECEIVING SPECIMEN AT THE HIV-1 PVL TESTING LABORATORY
Receiving lab to identify the specimen properly. If there is discrepancy in the test requisition
form versus the labeled tube, DO NOT PROCEED. Take corrective action to ensure that the
patients name and number on the request form are correct. In case of any confusion check
back with the collection site.
Receiving lab to check and thereby ensure at the time of specimen receipt that the
temperature of the specimen never exceeded 8C and the whole blood specimen was
not frozen, during storage at the collection site and transport to the testing site. Leakage
is also checked for.
In case, of any doubt send back the specimen and VL-1 form back to the COE, duly
signed by lab in-charge, with the COE technician. Another specimen must be collected
for PVL.
The receipt of the specimens to be duly documented on both the copies of the VL-1.
In case specimen is rejected, one copy of the VL-1 form with signatures of lab in charge
to be sent back with the center of excellence technician by hand on the same day.
Receiving lab to record the time/date of specimen receipt.
Do not freeze whole blood. Do not store whole blood for more than 6 hours after
collection-even at temperature range of 2-25 C. Plasma at the receiving lab has to be
separated from the whole blood within 2 hours of specimen receipt, within 6 hours of
specimen collection (i.e. by 4.00 P.M. on the same day Monday/Tuesday).
4.5.5 PROCESSING OF THE WHOLE BLOOD SPECIMEN IN THE RECEIVING LAB:
After preparation of DBS, the remaining whole blood specimen is be centrifuged for
separation of plasma as detailed below and processed further for estimation of HIV-1
PVL as per the instructions of the manufacturer of the kit being used.
o Separation of plasma from whole blood:
Centrifuge whole blood at 800 -1600 x g for 10 minutes at room temperature.
Remove the plasma and recentrifuge at 800 x g for another 10 minutes.
Aliquot and store 800-900l of plasma in a sterile 2 ml polypropylene

screw-capped tube.
In case of inadvertent delay, plasma specimen to be separated and stored at

2-8C overnight and transported to the testing site next morning at 2-8C for
performance of the test on the same day (to be processed for PVL within 24
hours after collection).
Plasma specimen is to be kept at 2-8C till processed.
Receiving lab must process the specimen within 24 hours after specimen collection.
The plasma specimen must be brought to ambient temperature before

performing the test as per the manufacturers protocol.
o Perform PVL assay as per manufacturers protocol on the available platform
4.6 FACTORS TO BE CONSIDERED WHILE INTERPRETING THE VIRAL LOAD

RESULTS:
The HIV-1 PVL quantification assay is influenced by many factors. Thus the interpretation
of absolute viral concentration measurement results is not straightforward. One important
issue to consider is whether measured change in viral load actually reflects a biological
event, or whether the change is within the variability limit of the assay. Repeat tests of
the same blood specimen can give results that vary by a factor of 3. This means that a
meaningful change would be a drop to less than 1/3 or an increase to more than 3 times
the previous viral load result. For example, a change from 200,000 to 600,000 is within the
normal variability of the test. A drop from 50,000 to 10,000 would be significant. However,
the most important change in a patient responding well/optimally to ART is reaching an
undetectable viral load level.
There is a considerable variation in the results of various types of assays used in
quantification of the same specimen but if performed proficiently, a commercial assay
shows reproducibility within approximately 0.2-0.5 log10, (varying in different regions of
the assays dynamic range). Daily variation in viral loads among clinically stable patients is
minimal at approximately 0.4 log10. Therefore a change in viral load, greater than 0.5 log10
RNA copies/ml (approximately 3-fold), exceeds assay and diurnal variations, and may be
considered to represent true biological events, while changes of less than 0.5 log10 cannot
be distinguished whether these are from random variability or a biological event. It is
important to note that in the low end of the dynamic range, assay variability has greater
impact on interpretation of absolute viral load change.
How are the changes in viral load measured?
Viral load changes are often described as log changes. This refers to scientific notation,
which uses powers of 10. For example, a 2-log drop is a drop of 102 or 100 times. A drop
from 60,000 to 600 would be a 2-log drop. Small changes of 10, 20, 30 copies are often not
considered to be a significant change in viral load and can reflect normal viral blips, not a
change in treatment response.
What do the numbers mean?

It is not known how long a HIV positive patient would stay healthy with any particular viral
load. All that is known so far is that lower PVL is better and seems to mean a longer, healthier
life. The viral load should drop to reach less than 50 copies within 6 months of ART. Even
when the HIV-1 viral load in a HIV positive is undetectable, the HIV virus can be passed on
to another person, although the risk is lower. There is no safe level of viral load.
4.7 LIMITATION OF VIRAL LOAD ASSAYS:
RNA assays used to measure PVL are perhaps most heavily relied upon in the medical
management of people diagnosed with AIDS and in people who test positive on the HIV-1
antibody tests. As many important clinical decisions are based on these tests, the highest
standards of sensitivity and specificity are recommended. There are however some concerns
with the viral load tests as given below:
Intra-assay and biologic variability may affect the findings.
The viral load test results can be unreliable if the body is fighting an infection, or if
the patient has just received an immunization. Blood should not be taken for a viral
load test within four weeks of any infection or immunization. Temporary increases
in viral load have been seen in these instances. Also, the physician must review
the patients adherence to the ART regimen and should postpone testing if recent
doses of ART have been missed that may cause rapid replication of HIV, in vivo. Such
patients may already be experiencing viral rebound and their ART therapy could be
incorrectly judged to be failing.
A drawback to PVL testing is the high cost of assays and requirement of technical expertise.
4.8 STANDARDIZATION OF HIV-1 PLASMA VIRAL LOAD REPORTING:
Laboratory reports of viral load assays should be standardized, accurate and adequate
for patient treatment and public health monitoring of the HIV infection and acquired
immunodeficiency syndrome (AIDS) epidemic. To ensure test report comparability among
laboratories, standard testing and reporting methods are needed; moreover, standardized
results are needed for early detection of treatment failure and early access to patient
care.
Required items to report
The laboratory should completely fill out the report found in Annex VII (a to d), as per
testing platform.
It should be duly signed in the VL-1 reporting format (See Annex VII (a to d))
It should be sent from the lab to the ART centre by courier by Saturday to reach the ART
centre latest by Monday. The courier will be paid from the contingency grant.
A copy of the report should be e-mailed to NACO by Saturday at drbbrewari@yahoo.

com and labservices.naco@gmail.com
4.9 Q UALITY ASSURANCE FOR HIV-1 PLASMA VIRAL LOAD TESTING:
Viral load testing is an integral part of the management of HIV disease. It is absolutely
imperative to ensure the accuracy, precision and reproducibility of the test results by
adhering to stringent Quality Assurance and Quality Control measures at all times.
Quality Assurance is defined as a set of planned and systematic activities to ensure adequate
confidence that requirements for quality will be met.
Internal Quality Control refers to those measures that must be taken to ensure that the
test is working, the technical aspects of the test procedure have been met/followed and
the results produced are valid within the limitation of the test system used. Laboratories
performing HIV-1 Viral load quantification need to use external quality control specimens in
addition to the controls contained in test kits for validation of the result.
It is recommended that a high positive control, low positive control and a negative control
that come with the test kits be included with each run. The copy number per ml for each
positive result should fall within the range of values indicated in the package insert. The
negative control should give a less than the lower detection limit result. If controls are
not as expected, the run is not valid and is to be repeated. These controls should meet
the prescribed regulatory requirements for such controls. It is good to have traceability
to international reference standards. Use of above test controls, that are used to validate
a test run and to quantitate HIV-I RNA, would however not validate the analytic testing
process which may include testing problems related to pipetting, inadequate incubation or
washing or variability in kit lot sensitivity.
4.9.1 INVALID TEST RUNS
When invalid positive or negative results are obtained on running internal controls, the run
is declared invalid and the entire test procedure for all the specimens has to be repeated in
another run by processing another aliquot of the original plasma specimens.
Flags and comments may be generated by the analyzer during the run. The operator must
check the run printout(s) for flags and comments to verify that the run is valid.
With the exception of instrument failures subsequent to the denaturation of amplicons,
an instrument failure during a test run as indicated by the system error messages also
constitutes an invalid test run.
4.9.2 INTERNAL QUALITY CONTROL (ASSAY CONTROLS-PART OF THE SYSTEM)
Controls are supplied by the manufacturer and are to be processed like patient
specimens. A low positive, high positive and a negative control are supplied with the
kit. Run controls to check accuracy and reproducibility.
All quality control failures must be logged and corrective action completed before
specimen analysis takes place.
All reagents used must be logged onto log sheets with the date opened, expiry date and
signature. Reagents discarded due to contamination, spillage, etc. must be logged in the
appropriate log sheets.
Reagents must be stored as recommended by the manufacturer and daily temperature

logs should be maintained.
Results should be entered onto Levy-Jennings plots to monitor any trends, shifts or bias
in results.
4.9.3 EXTERNAL QUALITY ASSESSMENT
Every testing facility must be able to demonstrate and document its competence in
performing the tests. External quality assessment (EQA) is an evaluation by an outside
agency of the performance of a laboratory on specially supplied small panels of well
characterized specimens. The objective is to achieve between-laboratory and between-
method comparability.
4.9.4 OBJECTIVES OF EQAS
The primary objective is to continually improve and maintain the high standard of
the laboratorys performance,
To continually institute a formal monitoring and evaluation programme,
To continually promote the concept of quality assurance, quality control, and quality
assessment in the laboratory,
To assess the quality of service of the participating laboratory,
To identify problems and take appropriate interventions for corrective actions,
To encourage the implementation of good laboratory practices, and
To provide teaching and training programs.
Participation in external quality assessment (EQA) is not a substitute to day to day internal
quality control practices. EQA is designed to assess the integrity of the entire lab testing
process. Even when all precautions have been taken to achieve accuracy and precision in
the laboratory, errors may arise which may be detected by objective external assessment.
The principle is that the assessed material (values are known) is sent from an international,
national or regional centre to a large number of participating laboratories at regular
designated intervals. The results produced by the participating laboratories are assessed for
accuracy, precision and reproducibility in a confidential manner by the lab conducting EQA.
The labs producing inaccurate results are revamped through training and troubleshooting.
The EQAS essentially contains the following components:
Filling up questionnaire to understand the laboratory capabilities and additional

requirements
Training for viral load estimation procedure and participation in EQAS
Processing of the specimens received under EQAS following the routine procedure
of viral load estimation
Submission of report to the EQA conducting laboratory
Doing analysis of results, assessment of performance and trouble shooting
4.9.5 EQA FOR HIV-1 PLASMA VIRAL LOAD TESTING
The NACO designated laboratories that will initiate/perform HIV-1 PVL testing for Second
line roll out are to participate in EQA being conducted by the centre listed below for the
time being:
RCPA (Royal College of Pathologists Australasia) Quality Assurance Programme
RCPA Quality Assurance Programmes Pvt Ltd was established by the Royal College
of Pathologists of Australasia in 1988 and is providing the EQA services to over 40 countries
and 4,000 programs around the world. RCPA Quality Assurance Program Pvt Limited is a
NATA (National Associated Testing Authority, Australia) accredited Proficiency Testing
provider for HIV-I RNA Viral load and complies with the requirements of ILAC G13. The
details for EQA are given at Annex- VIII
4.10 OPERATIONAL PLAN FOR HIV-1 VIRAL LOAD TESTING AND EQAS
It is proposed that HIV-1 viral load testing facilities for the National HIV/AIDS care and
treatment programme would initially be set up at select centers. The NACO labs that have
been identified to initiate and perform HIV-1 PVL testing for specimens being sent by the
NACO identified Second line centres are:
Kasturba Hospital for Infectious Diseases, Mumbai
Tuberculosis Research Centre (TRC), Chennai
Institute of Human Behavior and Allied Sciences (IHBAS), New Delhi
National Institute of Cholera and Enteric Diseases (NICED), Kolkata
Gandhi Hospital and Medical College, Hyderabad
St Johns Hospital, Bangalore
Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh
Institute of Medical Sciences (BHU), Varanasi
Biramjee Jeejeebhoy Medical College (BJMC), Ahmedabad
Regional Institute of Medical Sciences (RIMS), Imphal and
National AIDS Research Institute (NARI), Pune
NACO has created the following interim linkages until all the designated HIV-1 PVL testing
centres become operational:
The above linked centres, both the COEs and the testing labs, should coordinate their
collection days and times so that viral load specimens that are being sent from different
centres to the same lab can be coordinated to be processed together on the same day,
ensuring the efficient use of viral load reagents and laboratory time.
It is proposed to identify the eligible patients after a detailed examination by the SACEP. The
SACEP meeting will be held on Monday/Tuesday (or any designated day) morning between
9:00AM to 11:00AM depending on the convenience of the institution. Eligible candidates
will be subjected to HIV-1 PVL testing before SACEP takes the decision to initiate Second
line ART.
Blood specimen (4ml) will be collected in an EDTA vacuum evacuated tube immediately
after SACEP meeting and processed as given below:
In case the PVL testing lab is in the same city as the COE: whole blood specimen is to be
transported to the PVL testing lab at 2-8oC within a maximum of 6 hours after collection
In case the PVL testing lab is in a different city as the COE: the laboratory technician
at the COE will prepare, package, and store the DBS (Section 4.13) and separate the
plasma (as detailed above) within 2 hours after specimen collection. The plasma
specimen will be stored at 2-8oC until transported by the COE technician. The
specimen will be hand carried by the COE technician from COE to the PVL testing
laboratory as detailed above. The COE must ensure that the lab technician carrying
the specimens must leave the COE that same day.
Frequency and processing of specimen and transport details will be as detailed in Table 1
Once the specimens have been received at the PVL testing lab, estimation of HIV-1
PVL must be done within 24 hours after the specimen was collected.
The PVL testing lab must courier back the test reports to the corresponding COE by
the weekend. Cost of the same will be met from contingency grant.
To ensure the quality of the testing on a daily basis and to ensure that all labs meet
international testing standards, these centers would participate in EQAS for HIV-1 viral load
testing. An attempt is being made to provide EQAS specimens to all the NACO identified
testing labs for HIV-1 PVL testing. All labs must participate and provide necessary cooperation
for implementing the same.
The details of the EQAS process flow have been annexed at the end of the laboratory
guidelines for VL testing.
4.11 PRECAUTIONS AND SPECIFIC INSTRUCTIONS FOR REAGENTS AND

EQUIPMENTS:
4.11.1 GENERAL
Viral load assay is for in vitro measurement of plasma HIV-1 RNA copies and is not for
diagnostic use
Treat all specimens as potentially infectious. Adhere to Standard Work Precautions
when performing the assay.
Only personnel trained in handling infectious material should perform this procedure
Screw capped tubes must be used for processing specimens and controls to prevent
splashing and potential cross-contamination of specimens or controls. Do not use
snap-cap tubes. Handle all specimens or controls in accordance with the Good Lab
Practices in order to prevent cross-contamination
Do not pipette by mouth.
Do not eat, drink or smoke in laboratory work areas. Wear protective disposable gloves,
laboratory coats and eye protection when handling specimens and kit reagents. Wash
hands thoroughly after handling specimens and kit reagents
Avoid contact of these materials with the skin, eyes or mucous membranes. If contact
does occur, immediately wash with large amounts of water. Burns can occur if left
untreated. If spills of these reagents occur, dilute with water before wiping dry.
Avoid contaminating gloves while manipulating specimens
Specimens and controls should always be prepared in the laminar flow -failure to do
so may result in specimen contamination
Handle and manipulate specimens in a Class II Biological Safety Cabinet
Thoroughly clean and disinfect all work surfaces with a freshly prepared solution of
0.5% sodium hypochlorite and follow by wiping down the surface with 70% ethanol.
Any deviations from the specified procedures and guidelines may affect optimal assay
performance.
This test is for use with human plasma collected in EDTA anticoagulants only. Heparin
has been shown to inhibit PCR and must not be used with this procedure.
4.11.2 REAGENTS STORAGE AND USE
Store reagents strictly as per manufacturers specific reagent storage recommendations
Visually inspect each reagent bottle before use to ensure that there are no signs of
leakage and or abnormal colour.
Do not use a kit after expiry date. DO NOT interchange, mix or combine reagents
from kits with different master lot numbers. Ensure that all reagents used are of the
same master lot of reagents.
Add all reagents using a pipette capable of accurately delivering specified volumes.
Regularly calibrate pipettes for accurate delivery and maintain logs
Avoid microbial and ribonuclease contamination of reagents when removing aliquots

from reagent bottles. The use of sterile disposable pipettes and RNase-free pipette
tips is recommended.
Do not freeze reagents or controls
Do not pool reagents from different lots or from different bottles of the same lot.
4.11.3 EQUIPMENT
Perform manufacturer recommended maintenance and calibration of all equipment,

including pipettes to ensure proper functioning.
4.11.4 WORK AREAS
To minimize the possibility of lab areas becoming contaminated with the amplicon, the lab
area should be separated into several distinct areas organized around the pre-amplification
(separate reagent and specimen preparation areas) and post-amplification (Amplification
and Detection) areas. Personnel should use proper anti-contamination safeguards when
moving between areas.
Workflow in the laboratory must proceed in a uni-directional manner, beginning in

the Pre-Amplification Area and moving to the Post-Amplification (Amplification and
Detection) Area.
Pipettes and other supplies should be dedicated to a specific area. Specimens,

equipment and reagents should not be returned to the area where a previous step
was being performed and should not be used for other activities or moved between
areas
Pre-amplification activities must begin with reagent preparation and proceed to
specimen preparation.
Supplies and equipment must be dedicated to each pre-amplification activity and

not used for other activities or moved between areas. Equipment and supplies used
for reagent preparation must not be used for specimen preparation activities or for
pipetting or processing amplified DNA or other sources of target DNA
Gloves must be worn separately in each area and must be changed before leaving
that area.
The pre-amplification area should have a template free area for preparation of
reagents and an amplicon free area for specimen and control preparation
Post-amplification supplies and equipment must remain in the Post-Amplification
Area at all times
The post-amplification area should have analyzer(s) and Data station(s) with
additional area for preparing Working Amplification and Detection reagents.
4.12 TROUBLE SHOOTING:
While performing the viral loads in the lab, there will be occasions when things may
go wrong. The problems could occur because of mechanical, chemical or human
error. Staff should be trained to recognize when there is a problem and how to
correct them so that the final patient results sent out are not affected. Please follow
the manufacturers instructions for troubleshooting
Note: Adhere to standard work precautions and PEP as per NACO HIV testing. Keep eye
splashers, body showers and supply of running tap water within vicinity of the working lab
4.13 D BS COLLECTION FOR ALL PATIENTS UNDERGOING VIRAL LOAD TESTING
The national programme will collect DBS samples from all patients who are sent for Viral
load. The consent form is as annex IV (integrated consent for 2nd line ART as well as for
collection of blood for storage)
The purpose of this collection and storage of blood on Dried Blood Spots (DBS) from
patients undergoing evaluation for Second-line ART in India, is to subsequently conduct
HIV genotypic resistance testing on these specimens to evaluate the patterns of HIV drug
resistance that have developed among patients who have developed treatment failure to
the standard First-line ART regimen. Clinical and laboratory data will be abstracted from
patient records to further analyze and correlate HIVDR findings with virologic, immunologic,
and clinical outcomes of patients receiving Second-line treatment. Overall, the findings of
these analyses can be used to guide the expansion of ART services, and specifically Second-
line ART services, in India.
The objective of the analysis will be:
1. To determine the patterns of HIV-DR that are present among patients who have
developed treatment failure to the standard First-line regimen,
2. To determine if HIV-DR patterns at therapy switch have an impact on virologic suppression

at 6 months and/or 12 months among patients who receive Second-line therapy, and
3. To evaluate the clinical, immunologic, and survival outcomes of patients who

developed failure to First-line ART at 12 and 24 months. This analysis can be stratified
by HIV RNA at the time of initial Second-line evaluation (<400 copies/mL, 401-5,000
copies/mL, >5,000 copies/mL)
4.13.1 SPECIMEN COLLECTION, PROCESSING, AND STORAGE:
Blood is routinely collected from patients at the time of evaluation for Second-line ART at
the SACEP (COE) for HIV RNA, chemistry panel, liver function tests, and complete blood
count. At this time, a dried blood specimen (DBS) will also be collected.
Specimen collection:
DBS should only be made from patients blood tubes that have been specifically
labelled or marked as eligible. Before the DBS is made, the DBS-ID and ART-ID for the
participant should be written on the filter paper card. Anti-coagulated blood should
be spotted onto filter paper within 24 hours of collection. The filter paper should
be handled only at the edge; the areas that will be used to collect specimens should
not be touched. A filter should only be spotted with the blood of a single patient.
For recently collected, fresh whole blood, invert the blood collection tube 2-3 times to mix
the whole blood. Carefully open the blood collection tube. Use a pipette (with disposable
tip) to aspirate 100 l of whole blood and apply it to the centre of one pre-printed circle to
fully saturate the circle.Repeat this procedure to fill each circle on the card with blood. For
each specimen at least four saturated circles should be obtained. Opening of the tubes and
pipetting should be performed following standard laboratory biosafety precautions.
Specimen drying:
Avoid touching the part of the card with the blood spot. . Dry all specimen cards at least
4 hours at ambient temperature in a suspended horizontal position. Depending on the
climate it might be necessary to allow spots to dry over night. Do not use oven to fasten
the drying time of the cards. When dry, the spots should be a uniform dark brown. The
appearance should be similar to that of a dried bloodstain and no areas of red coloration
should be seen.
Specimen packaging:
Make sure the DBS or DPS are completely dry before packing. Packaging of each DBS card into
a separate gas-impermeable zip-lock bag with 2-3 desiccant packs (to remove any residual
moisture from the cards) per bag and a humidity indicator card (to indicate the relative
humidity inside the bag) is recommended. When packing, make sure that the humidity
indicator cards are faced outside. Place the front of the humidity indicator card facing outside
so that the markings are clearly visible. Press the bag with both hands to squeeze out the air
from the bag and then seal it. Place 5-10 of the above small bags into a large plastic bag. In the
large plastic bag, also place a printed manifest with specimen information. Plastic or foil bags
used for storage must be gas impermeable to keep the contents of the bag humidity-free. Bags
available from grocery stores or other outlets that do not sell scientific supplies are inadequate.
Humidity indicator cards and desiccant packs have a color indicator which changes from blue
to pink as humidity increases. All humidity indicator and desiccants should be replaced with
fresh material before they have all changed to a pink colour. To ensure proper packaging of
the DBS cards, the humidity indicator card should be examined once a week if the sample
is kept at room temperature. Before placing desiccant packs into a zip-lock bag with DBS,
make sure desiccant packs have remained dry during storage (indicator card should show
blue color). When an indicator is beginning to change, it is time to change the humidity
indicator and desiccant packs. Desiccant packs can become moist after use with DBS, but
also after storage in a humid environment. Store desiccant packs with humidity indicator
cards to evaluate whether their moisture level has become too high. Humidity cards and
desiccant packs can be re-used. Moist humidity indicator cards and desiccant packs should
be dried in a 65C oven over night until the colour indicator returns to blue. Remove from
the oven and store in a sealed bag with a humidity indicator card until reuse or until they
once again need to be dried in the oven.
Specimen storage:
For short-term storage (preferably two weeks maximum, but no more than 30 days) at the
collecting sites, DBS can be kept in the gas impermeable zip-lock bags with desiccants and
stored at room temperature. DBS held at room temperature should be stored in a box or
container so that direct light will not damage them. DBS should be examined frequently
(e.g., weekly) to evaluate whether the 30% circle in the humidity indicator card has changed
to a pink color; when it does, the desiccants must be changed immediately.
DBS can be kept at room temperature or at 4C only for short term storage (<30 days). DBS
should not be frozen at the collection site unless definite arrangements can be guaranteed
to maintain them in a frozen state until they reach the genotyping laboratory. In settings
where constant refrigeration may not be possible because of frequent electricity outages, or
where high humidity is likely within the available refrigerator/freezer, it is preferable to hold
the DBS at room temperature. If possible, DBS should not remain at a collecting site with
limited storage conditions for more than 7 days before being transported to a laboratory
with a constant electricity supply and a refrigerator or freezer in which the humidity has
been evaluated and confirmed as suitable for long-term storage of DBS.
For long term storage (>30 days), DBS should be transported to a central facility where
there is a constant electricity supply in a freezer at 20C or below that has been evaluated
and confirmed as suitable for long term storage of DBS. If frozen, DBS should only be taken
out of cold storage when they are being transported to a reference laboratory or tested.
Specimen Transport
DBS should be transported to the regional or national genotyping laboratory using the
quickest and reliable arrangements. Unless humidity at the blood draw site is substantially
higher than in the processing laboratory, and provided suitable storage boxes are available
at the site to keep DBS from light and contamination, no special arrangements need be
made to transport DBS more often than weekly.
For specimens that have been stored at room temperature: The desiccants in the specimens
bags should be changed before transport for DBS specimens that have been stored for
longer than 7 days at the collection site. This should be done even if the indicator remains
blue. Reseal the bag and transport specimens by the fastest means using courier service or
through the postal system (preferably with expedited service and a guaranteed delivery) at
room temperature.
For specimens that have been stored at 4oC: Remove the bagged specimens from the
refrigerator and allow them to reach room temperature before opening the bag. Once the
sealed bag has equilibrated, open it and remove the old desiccants. Add fresh desiccants
and reseal the bag. Transport the bag by the fastest means. If a cooler is available for
transport this will protect specimens from short periods of high temperature.
For specimens have been frozen at -20oC or -70oC: These specimens should be transported
on dry ice or liquid nitrogen. Thawing of frozen DBS specimens should be avoided if possible.
A cooler is not sufficient to maintain them in a frozen state.
All DBS specimens should be logged into the survey system (whether it is a notebook or a
computer software package). The log should include notes on specimen quality and packaging.
The logbook should include a record of eligible specimens for which there is no DBS material
available to be sent to the genotyping laboratory, and the reason. An acknowledgement
or notification system should be set up involving the survey coordinator, the transport
system, and the receiving genotyping laboratory, to ensure all DBS are delivered promptly
to genotyping lab and arrive in good condition. Either email or fax notification using the
shipping manifests may be used for this purpose. DBS should be re-examined for packaging
and specimen quality on arrival in the genotyping laboratory and recorded in the genotyping
laboratory.
Every ART centre shall be linked to a VL lab for which instructions will be given by NACO
to send the DBS filter paper to the corresponding HIV drug resistance genotyping national
reference labs.
ANNEXURE
ANNEX I:
SEVERITY GRADING OF SELECTED CLINICAL AND LABORATORY TOXICITIES
(source: Division of AIDS, National Institute of Allergy and Infectious Diseases, USA
Modifies,)
For abnormalities NOT found elsewhere in the toxicity table use the scale to estimate
grades of toxicity.
GRADE 1 Transient or mild discomfort; no limitation of activity; no medical intervention/

therapy required.
GRADE 2 Mild to moderate limitation of activity; some assistance may be needed; no or

minimal medical intervention/therapy required.
GRADE 3 Marked limitation of activity; some assistance usually required; medical

intervention/therapy required; hospitalization possible.
GRADE 4 Extreme limitation of activity; significant assistance required; significant medical

intervention/therapy required; hospitalization or hospice care.
HAEMATOLOGY GRADE 1 GRADE 2 GRADE 3 GRADE 4

Haemoglobin 8.0 9.4 g/dl 7.0 7.9 g/dl 6.5 6.9 g/dl <6.5 g/dl OR
OR 80-94 g/l OR 70-79 g/l OR 65 - 69 g/l <65 g/l OR <4.03
OR 4.93 5.83 OR 4.31 4.92 OR 4.03 4.30 mmol/l
mmol/l mmol/l mmol/l
Absolute neutrophil 1000 1500/ 750 999/mm 500 749/mm <500/mm OR
count mm OR 1.0 OR 0.75 .99/ OR 0.5 0.749/ <0.5/G/1*
1.5/G/1* G/1* G/1*
Platelets 75000 99000/ 50000 74999/ 20000 49999/ <20000/mm OR
mm OR 75 mm OR 50 mm OR 20 <20/G/1*
99/G/1* 74.9/G/1* 49.9/G/1*
CHEMISTRIES GRADE 1 GRADE 2 GRADE 3 GRADE 4
SODIUM
Hyponatraemia 130 135 meq/I 123 129 meq/I 116 122 meq/I <166 meq/I OR
OR 130 135 OR 123 129 OR 116 122 <116 mmol/l
Hypernatraemia 146 150 meq/I 151 157 meq/I 158 165 meq/I >165 meq/I OR
OR 146 150 OR 151 157 OR 158 165 >165 mmol/l
POTASSIUM
Hyperkalaemia 5.6 6.0 meq/I 6.1 6.5 meq/I 6.6 7.0 meq/I >7.0 meq/I OR
OR 5.6 6.0 OR 6.1 6.5 OR 6.6 7.0 >7.0 mmol/l
Hypernatraemia 3.0 3.4 meq/I 2.5 2.9 meq/I 2.0 2.4 meq/I <2.0 meq/I OR
OR 3.0 3.4 OR 2.5 2.9 OR 2.0 2.4 <2.0 mmol/l
BILIRUBIN
Hyperbilirubin-armia >1.0 1.5 x ULN >1.5 2.5 x ULN >2.5 5.0 x ULN >5.0 x ULN
GLUCOSE
Hypoglycaemia 55 64 mg/dl 40 54 mg/dl 30 39 mg/dl <30 mg/dl OR
OR 3.01 3.55 OR 2.19 3.00 OR 1.67 2.18 <1.67 mmol/l
Hyperglycaemia 116 160 mg/ 161 250 mg/dl 251 500 mg/dl <500 mg/dl OR
(nonfasting and no dl OR 6.44 8.90 OR 8.91 13.88 OR 13.89 27.76 <27.76 mmol/l
prior diabetes) mmol/l mmol/l mmol/l
Triglycerides 200 399 mg/ 400 750 mg/ 751 1200 mg/ <1200 mg/dl OR
dl OR 2.25 4.51 dl OR 4.52 8.47 dl OR 8.48 <13.55 mmol/l
mmol/l mmol/l 13.55 mmol/l
creatinine >1.0 1.5 x ULN >1.5 3.0 x ULN >3.0 6.0 x ULN >6.0 x ULN
TRANSAMINASES
AST (SGOT) 1.25 2.5 x ULN >2.5 5.0 x ULN >5.0 10.0 x >10.0 x ULN
ULN
ALT (SGPT) 1.25 2.5 x ULN >2.5 5.0 x ULN >5.0 10.0 x >10.0 x ULN
ULN
GGT 1.25 2.5 x ULN >2.5 5.0 x ULN >5.0 10.0 x >10.0 x ULN
ULN
Alkaline Phosphatase 1.25 2.5 x ULN >2.5 5.0 x ULN >5.0 10.0 x >10.0 x ULN
ULN
Pancreatic enzymes
Amylase >1.0 1.5 x ULN >1.5 2.0 x ULN >2.0 5.0 x ULN >5.0 x ULN
Pancreatic amylase >1.0 1.5 x ULN >1.5 2.0 x ULN >2.0 5.0 x ULN >5.0 x ULN
CHEMISTRIES GRADE 1 GRADE 2 GRADE 3 GRADE 4
TRANSAMINASES
Lipase >1.0 1.5 x ULN >1.5 2.0 x ULN >2.0 5.0 x ULN >5.0 x ULN
Lactate <2.0 x ULN with- >2.0 x ULN with- Increased Increased lactate
out acidosis out acidosis lactate with pH with pH <7.3
<7.3 without with life- threat-
life- threatening ening conse-
consequences quences
GASTRO- INTESTINAL GRADE 1 GRADE 2 GRADE 3 GRADE 4
Nausea Mild OR transient; Moderate Severe discom- Hospitalization
reasonable intake discomfort OR fort OR minimal required
maintained intake decreased intake for >3
for <3 days days
Vomiting Mild OR tran- Moderate OR Severe vomit- Hypotensive
sient; 2 3 persistent; 4 5 ing of all foods/ shock OR hos-
episodes per day episodes per day fluids in 24 hours pitalization for
OR mild vomiting OR vomiting last- OR orthostatic intravenous Rx
lasting < 1 week ing >1 week hypotension OR required
intravenous Rx
required
Diarrhoea Mild OR tran- Moderate OR Bloody diarrhea Hypotensive
sient; 3-4 loose persistent; 5 - 7 OR orthostatic shocks OR
stools per day loose stools per hypotension OR hospitalization
OR mild diarrhea day OR diarrhea >7 loose stools/ required
lasting < 1 week lasting > 1 week day OR intrave-
nous Rx required
RESPIRATORY GRADE 1 GRADE 2 GRADE 3 GRADE 4
Dyspnoea Dyspnoea on Dyspnoea with Dyspnoea at rest Dyspnoea requir-
exertion normal activity ing O therapy
URINALYSIS GRADE 1 GRADE 2 GRADE 3 GRADE 4
Proteinuria
Spot urine 1+ 2+ or 3+ 4+ Nephrotic syn-
drome
24 hours urine 200 mg to 1 1 g to 2 g loss/ 2 g to 3.5 g loss/ Nephrotic syn-
g loss/day OR day OR 0.3% to day OR >1.0% OR drome OR >3.5 g
<0.3% OR <3 g/l 1.0% OR 3 g to >10 g/l loss/day
10 g/l
Gross haematuria Microscopic only Gross, no clots Gross plus clots Obstructive
MISCELLANEOUS GRADE 1 GRADE 2 GRADE 3 GRADE 4
Fever (oral, >12 37.7 38.5 C OR 38.6 39.5 C OR 39.6 40.5 C OR >40.5 C OR >105
hours 100.0 101.5 F 101.6 102.9 F 103 105 F F for > continu-
ous hours
Headache Mild; no Rx re- Moderate OR Servere OR re- Intracable
quired non-narcotic sponds to initial
analgesia Rx narcotic Rx
Rash hypersesnitiv- Erythema, prui- Diffuse maculo- Vasiculation OR ANY ONE OF:
ity tus papular rash OR moist desquama- muscous mem-
dry desquama- tion OR ulcer- brane involve-
tion ation ment, suspected
Stevens-Johnson
(TEN), erythema
multiforme, ex-
foliative derma-
tistis
Fatigue Normal activity Normal activity Normal activity Unable to care
reduce by <25% reduce by <25 reduce by >50%: for self
50% cannot work
ANNEX II:
Request/Reply form to SACEP for review of patients suspected of treatment failure (to
be sent with patient records)
RRF: Request form to SACEP at COE /pCoE/ART plus Centre for Review
Dear Dr . Referral date.
Centre of Excellence /ART plus Centre
I would like to refer this patient for review by the SACEP for
Alternative First-line ARV ART drugs
Suspect Treatment Failure
Others (specify).
Name......................................... Age-
Sex..................
Name of the Care giver ..............................................................................................
Address & Phone no. ....
...
................................................................................................................................
ART centre name & phone no. .................................................................................
Contact person at ART centre&mobile no.
........................................................
Name & Contact no. of Linked NGO/CCC /DLN:
The following are attached with this request form:
Photocopy of the Patient treatment record(White Card)
Photocopy of all lab tests including CD4
Photocopy of all other relevant material
Photo documentation of toxicity ( If available)
Address proof with photo
The following sections summarize the patient antiretroviral therapy history:
A: Summary of the case history of the patient (pre-ART; ART; suspected treatment
failure/suspected ARV toxicity)
.............................................
B. Summary of adherence history and other psycho-social issues
.............................................
C. Summary of relevant laboratory tests including CD4 (of last 1 month) /viral load (if
available)
................................................
Name and Signature of Nodal Officer of referring
ART centre with contact number & email
Reply from SACEP at CoE/pCoE/ART plus Centre to Referring ART centre (After review)
Dear Dr Date....
ART centre..
Patient name..............Gender/Age..................
Address..................... SACEP registration no.

Referred for..................on Date............

.....
Findings/investigation
results:.............................................
..
Treatment/follow-up Plan:.
Name and Signature of Nodal Officer
COE/ART plus with contact number & e-mail
ANNEX III:
CF Consent form for patients starting Second line ART at COE
Consent form for patients starting Second line ART

I, (name), (address) .................................
CONSENT to share all information pertaining to my health and HIV/AIDS status with the
service providers who will be part of the management of my condition.
And
I AGREE to receive the Second line antiretroviral therapy.
I fully understand the information that has been provided by the health care staff in the following:
That Second line ART is not an emergency and thus will be started as per the deci-
sion of the doctor .I shall attend the ART centre as per appointment for timely initia-
tion of ART and regular follow up
That receiving Second line ART involves shared confidentiality with other service
providers such as CBO/NGO/CCC/positive network who may conduct outreach and
home-based care activities at home
That Second line ART requires 100% adherence to drugsand I shall abide by the same.
That there is no third line ART available in the programme
That I understand the side effects of Second line ART
That I shall not stop the drugs on my own and will return to the centre if there is
any problem
That the national programme shall collect and store my blood to find out if the ART
medicines are working against the HIV at a later date (Drug resistance testing etc).
This will not affect my current treatment. This will help the doctors to improve the
care and treatment of all patients undergoing treatment at this centre, and possi-
bly at other centres in the country.
Signature of witness Signature of patient with date
(Doctor/nurse/counselor)
(This should be translated in local language &/or explained for patient understanding
before taking patients signature)
ANNEX IV:
Drug information on Second line ARVs
LPV/r drug-drug interactions
Class Protease inhibitor (PI)

NACO Formulation Heat stable tablet: 200 mg LPV + 50 mg RTV
Contraindication LPV/r is contraindicated in patients with known hypersensitivity to
LPV or RTV
Safety in pregnancy No data on LPV/r in pregnant women. LPV/r should not be used
during pregnancy and breastfeeding.
Precautions Hepatic impairment avoid if severe renal impairment,
pregnancy; breastfeeding.
Food Should be taken with food
Interactions If ddI or antacids are administered, they should be taken at least 1
hour apart
LPV should not be taken with these drugs: amiodarone, astemizole,

cisapride, ergotamine and similar alkaloids, flecanide, garlic
supplements, lovastatin,midazolam, pimozide, propadenone,
rifamipicin, simvastatin, St Johns wort, terfenadine and triazolam
Rifamipicin should not be used in combination with LPV/r because

co-administration may cause large decreases in LPV concentrations.
LPV levels are increased by delavirdine and Ritonavir (RTV)
LPV levels are decreased by amprenavir, carbamazepine,

dexamethasone, Efavirenz, ketoconazole, nevirapine, Phenobarbital,
St Johns wort, phenytoin, rifamipicin and TDF.
LPV increases the levels of amiodaron, amprenavir, atorvastatin,

bepridil, calcium channel blockers, clarithromycin, ketoconazole,
indinavir, itraconazole, lidocaine (systemic), quinidine, rifabutin,
saquinavir, sildenafil and TDF.
LPV decreases the levels of amprenavir, atovaquone and methadone.
LPV has potential interactions with anticonvulsants, statins, oral

contraceptives, tricyclic antidepressants, oral anticoagulants and
immunosuppressants.
Adverse effects GI-related: diarrhoea, nausea, vomiting, colitis, abdominal discom-
fort, asthenia, headache, insomnia, rash.
Less frequently: drug mouth, hepatic dysfunction, pancreatitis,

dyspepsia, dysphagia, oesophagitis, influenza-like syndrome,
appetite changes, hypertension, palpitations, thrombophlebitis,
vascultitis, chest pain, dyspnoea, agitation, anxiety, ataxia, hypertonia,
confusion, depression, dizziness, dyskinesia, parasthesia, peripheral
neuritis, somnolence; Cushing syndrome, hypothyroidism, sexual
dysfunction, anaemia, leucopenia, dehydration, oedema, lactic
acidosis; arthralgia, myalgia, abnormal vision, otitis media, taste
disturbances, tinnitus, acne, alopecia, drug skin, pruritis, skin
discoloration, nail disorders, sweating; Lipodystrophy and metabolic
effects, raised bilirubin and lowered sodium,low platelet and low
neutrophil counts also reported in children.
Storage Room temperature (below 30 degrees)
Lamivudine (3TC)
Class Nucleoside reverse transcriptase inhibitor (NsRTI)

NACO Formulation Combined as fixed dose combination as TDF/3TC at dose of 300
mg once a day
Contraindication Known sensitivity to 3TC
Safety in pregnancy Limited data available on safety of 3TC in human pregnancy
Precautions Renal impairment
Hepatic impairment: potentially life-threatening lactic acidosis and

severe hepatomegaly reported, caution in liver disease. Recurrent
hepatitis may occur in patients with chronic hepatitis B infection
on discontinuation of 3TC
Food Can be taken with or without food
Interactions Rare
Adverse effects Nausea, vomiting, diarrhoea, abdominal pain, cough, headache,
fatigue, insomnia, malaise, fever, rash, alopecia, muscle disorders,
nasal symptoms; peripheral neuropathy reported; rarely pancrea-
titis; neutropenia, anaemia, thrombocytopenia; lactic acidosis/
hepatic steatosis; raised liver enzymes and serum amylase
Storage Room temperature (15-30 degrees C)
ATV/r drug-drug interactions
Class Protease inhibitor (PI)

NACO Formulation Atazanavir 300mg and ritonavir 100mg
Contraindication ATV/r is contraindicated in patients with known hypersensitivity
to ATV or RTV
Safety in pregnancy No data on ATV/r in pregnant women. However, its efficacy in
pregnancy is less than LPV/r.
Precautions Hepatic impairment avoid if severe renal impairment.
Food Should be taken with food
Interactions In case of regimen IV/IVa
1. H2 receptor antagonist dose should not exceed a dose equiva-
lent to Famotidine 40 mg BID in ART-nave patients or 20 mg
BID in ART-experienced patients.
2. Give ATV 300 mg + RTV 100 mg simultaneously with and/or >10
hours after the H2 receptor antagonist.
Example:If a PLHIV onZidovudine + Lamivudine + Atazanavir/Rito-
navir(Regimen IV) requires to be treated with Famotidine 20 mg
BID or Ranitidine 150 mg BID, S/he should be instructed to take
Tab. Famotidine/Ranitidine withZidovudine + Lamivudine at 8.00
AM and in evening give ZL and ATV/r at 8 p.m. and ensure that
there is a gap of at least 2 hours before or 1 hour after Famotidine/
Ranitidine evening dose.
In case of Second line Regimen V (Tenofovir + Lamivudine +Ata-
zanavir/Ritonavir):
1. PPIs should not exceedthe dose of Omeprazole 20 mg daily or
equivalent dose of Esomeprazole 20mg/Pantoprazole 40 mg/
Rabeprazole 20 mg in PI-nave patients, along with Ritonavir
boosted Atazanavir. PPIs should be administered at least 12
hours prior toAtazanavir/Ritonavir.
2. PPIs are not recommended in PI-experienced patients.
Example: If a PLHIV is onTenofovir + Lamivudine + Atazanavir/
Ritonavir requires to be treated with PPI, S/he should be instruct-
ed to take Tab. Omeprazole 20 mg/Esomeprazole 20mg/Panto-
prazole 40 mg/Rabeprazole 20 mg OD at 8 AM andTenofovir +
Lamivudine +Atazanavir/Ritonavirafter 8 PM.
H2 receptor antagonists are not recommended with Tenofovir +

Lamivudine +Atazanavir/Ritonavir combination.
Adverse effects Apart from the PI-class specific side-effects like hyperglycaemia,
fat maldistribution, hyperlipidaemia (especially with Ritonavir
boosting). The unique side-effects of Atazanavir includeindirect
hyperbilirubinaemia (producing yellow discolouration of eyes),
skin rash, prolongation of PR interval and nephrolithiasis.
Prolongation of P-R and Q-Tc interval in the ECG can occur.
So PR interval need to be monitored in patients with known
conduction defects or with concurrent use of other drugs that
alter conduction abnormalities (like diltiazem, clarithromycin,
cisapride, ketoconazole etc.). However, routine ECG before
starting Atazanavir based ART is not recommended.
Atazanavir induced urolithiasis is also reported; presumably due
to precipitation of the drug resulting in crystalluria in a manner
analogus to Indinavir.
Storage Room temperature (below 30 degrees)
Rifabutin
Class Anti-tuberculous agent

NACO Formulation Tablet 150 mg
Concurrent use with ATV/r (no change) , Rifabutin dose 150 mg
once daily 3x/wk
Rifabutin AUC by 303%
Contraindication Allergy to rifampicin
Safety in pregnancy Limited data in pregnancy. Not teratogenic in rats/rabbits
Precautions Allergy to rifamipicin
Food none
Interactions Rifabutin reduces levels of warfarin, barbiturates, benzodiazepines,
beta-blockers, chloramphenicol, clofibrate, oral contraceptives,
corticosteroids, cyclosporine, diazepam, dapsone, digitalis, doxycycline,
haloperidol, oral hypoglycaemics, ketoconazole, methadone,
phenytoin, quinidine, theophylline, trimethoprim, verapamil.
Drugs that inihibit cytochrome P450 and prolongs the half life of
Rifabutin: PIs and Delavirdine, erythromycin, clarithromycin (56%
increase), and azoles (fluconazole, itraconazole, ketoconazole).
Adverse effects Common: brown-orange discoloration of secretions: urine,
tears, saliva, sweat, stool, skin. Infrequent: Rash, GI intolerance,
neutropenia. Rare: flu-like illness, hepatitis, hemolysis, headache,
thrombocytopenia, myositis.
Uveitis is dose-related (usually> 450 mg/day) or with standard
300mg/day combined with drugs that increase rifabutin levels
(most PIs, clarithromycin, fluconazole)
Storage Room temperature (15-30 degrees C)
.
ANNEX V:
Recommendations for Co administering Antiretroviral Drugs with RIFABUTIN 2007
Non-nucleoside reverse-transcriptase inhibitors
Antiretroviral Rifabutin dose
Comments
dose change change
Rifabutin AUC by 38%. Effect of
Efavirenz + protease inhibitor(s)
___ to 450-600
on Rifabutin concentration has not
Efavirenz No change mg (daily or in-
been studied. Efavirenz should not
termittent)
be used during the 1st trimester of
pregnancy.
No change (300
Rifabutin and Nevirapine AUC not
Nevirapine No change mg daily or
significantly changed.
thrice-weekly)
Dual protease inhibitor combinations
Antiretroviral Rifabutin dose
Comments
dose change change
___ to 150 mg
Lopinavir/ Rifabutin AUC by 303%; 25-O-des-
No change every other day
ritonavir ) acetyl Rifabutin AUC by 47.5 fold.
or 3x/week
Ritonavir (any
dose) with
saquinavir,
indinavir, am- ____ to 150 mg
Rifabutin AUC and 25-O-des-acetyl
prenavir, fos- No change every other day
rifabutin AUC , by varying degrees.
amprenavir, or 3x/week
atazanavir,
tipranavir or
darunavir
ANNEX VI:
Treatment education information for Second line ART patients
REMEMBER THAT
If you miss doses (even 2 dose in a month) FURTHER DRUG RESISTANCE will
develop. This is bad for you as these Second line drugs will stop working.
Drugs must be taken as prescribed with food, and do not miss any dose
If you forget a dose, do not take a double dose.
If you stop taking the ART, you will become ill within months.
Do not share any of the drugs with your spouse, family
or friends.
If you find it difficult to take your pills, go back to
the ART center and discuss this with the doctor and
counselor. Ask for support from your treatment
supporter, family, friends, NGO and positive network.
Remember : Adherence is under your control
Note: The color, shape and size of ARV drugs may be different due to different supplier each year.
It is common to have side effects. They will usually go away in a few

weeks. You can ask doctor to give you some medication to help you
make it better. If you have side effects, do the following:
If you have Do the following

Nausea Take the ARV pills with food.
Diarrhoea Keep drinking and eating, do not eat spicy
food/chilies.
Muscle pain, fatigue These will go away.
I nausea or diarrhea persists or gets worse, report to the ART center.
Seek care urgently if:
Yellow eyes with high fever, headache, running nose and body ache.
Missed periods/possibility of pregnancy.
Severe abdominal pains.
Extreme paleness of face, hands or eyes.
Fatigue and shortness of breath.
Note: Remember to take your cotrimoxazole prophylaxis tablet every day, if the doctor
prescribes it.
Always use condom during sex.
Do not stop any drugs by yourself.
Phone: Call ART centre if you have any questions or
problems. (9 AM 4 PM)
Phone: After 4 PM, Contact the hospital Emergency number.
Phone: Call the local positive network number for support.
National AIDS Control Organisation

Ministry of Health & Family Welfare
Government of India, 9th Floor, Chandralok Building
26, Janpath, New Delhi 110001, India
Tel: 011-23325343, 011-23731774, 011-23731778,
Fax: 011-23731746
E-mail: info@nacoonline.org
ANNEX VII (A) VIRAL LOAD TEST REQUISITION FORM
Annex VII (a)-Viral Load Test Requisition Form
VL-1 National AIDS Control Organization Accession Number
Page-1 HIV-1 Plasma Viral Load Test Reauisition Form For Testing Lab Use Only
To be filled out by the MO/Nurse/Lab technicion

ART Center Information Patient Section
Name: : _________________
ART Center Name Patient ID # : ___________________
Address : _______________________ Patient Name : _________________
District : _________ State : _________ Sex : M / F
Telephone # : ____________________ Age : ____________
Previous HIV-1 Plasma Viral Load Test Results from ART Center
Baseline : 6 Months: Other (please Explain ):
Relevant Clinical Details
Latest CD4 Count,with date : _____________________________
Earlier HIV-1 PVL Test Performed ? Y / N Date Of Earlier HIV-1 PVL : ____ ____ _____
dd mm YY
Result of Earlier HIV-1 PVL Testing (If Performed ) : _____________________________________
Manufacturer Of Previous HIV-1 PVL Test : __________ Assay/Kit used : ___________________
Any infection or immunization in the past 4 weeks ? Y / N

HIV-1 PVL Specimen Collection
Collection Date : _______ ________ _______ Collection Time : _______________
Date Month Year
Name Of MO/Nurse?Lab Technician : _______________ Signature : ________________________
Signature Of ART Nodal Ocer : ____________________ Stamp :__________________________

To Be filled out by the ART lab technician carrying the specimens
For Lab Technician Couriering the Specimen
Name of Lab Technician In-Charge : ___________________________________________________
Name of ART Center : _______________________________________________________________
Date Of Specimen Transport to Lab : ______ _____ _____ Time Of Departure : ________
Day Month Year
Signature :
To Be filled out by laboratory - For Laboratory Use Only
Date Specimen Received ( dd/mm/yy):________________ Time Received : _____________
Specimen received in the acceptable condition : Y / N (Please Circle )

If No,list the state of specimen received :
Unlabeled/Mislabeled/Insucient/Inappropriate/Invalid/Other
Stamp:
Name Of Lab In-Charge : ________________________
Signature : ____________________________________
ANNEX VII (B) COBASAMPLICOR REPORTING FORMAT
Annex VII(b) - Cobas Amplicor Reporting Format

VL-1 Lab Name
Page 2 Address (Street ,District,State)
Lab Phone Number
HIV-1 Plasma Viral Load Result Form

Cobas Amplicor
Accession Number/Lab Registration Number : ________________________________
Patient ID Number : _______________________________________________________
Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):____________
Test Kit Name : Cobas Amplicor HIV-1 Monitor Test ,Version 1 Manufacturer : ____________
Version : _______________________
Result
HIV-1 RNA Copies/ml
Log-Transformation :
Notes : HIV-1 Quantization by Cobas Amolicor

Human Immunodeciency virus(HIV) is the etiologic agent of Acquired immunodeency Syndrome(AIDS).
Quantitative measurements of HIV Viremia in the peripheral blood have shown that higher virus levels
may be correlated with increased risk of clinical progression of HIV Disease.
Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations as 50
RNA copies/ml to 750,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and
have been documented in the plasma of uninfected persons or persons infected with other RNA viruses
that resamble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a
specimen of a patient not conrmed as being infected with HIV(through EIA,Western Blot,Or HIV DNA
Assays).
The minimum reliable and signicant change in measurement(as compared to baseline value or
previous test value)is a 3-fold(0.5 log) change.
Recommendations:A positive viral load result must always be correlated with clinical hitory and HIV
status of the patient.The cobas Amplicor HIV-1 Monitor test 1.5 is not intended to be used as a diagnostic for
HIV-1 infection.This test is not intended for HIV-2 Patients. It is recommended that the follow up viral load tests
be repeted at the same laboratory with the same technique/procedure in order to caompare changes in subsequent.
Name Of lab in-charge : ________________________ stamb of lab in-charge :
signature Of lab In-charge : __________________
Not valid for medical legal purposes
ANNEX VII (C) TAQMAN REPORTING FORMAT
Annex VII(c) - Taqman Reporting Format
VL-1 Lab Name
Lab Phone Number

Cobas Taqman
Accession Number/Lab Registration Number : _________________________________________
Patient ID Number : ________________________________________________________________
Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):____________
Test Kit Name : Cobas Taqman HIV-1 Test Manufacturer : _____________

Version : _______________________
Result
HIV-1 RNA Copies/ml
Notes : COBAS TaqMan HIV-1 Test

Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations low as 47
RNA copies/ml to 10,000,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and
that resemble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a
Assays).
The minimum reliable and signicant change in measurement(as compared to baseline value /
status of the patient.The cobas Taqman HIV-1 test 1.5 is not intended to be used as a
dianostic test for hiv-1 infection.This test is not intended for HIV-2 Patients.
It is recommended that viral load tests be repeted at the same laboratory with the same
technique/procedure in order to caompare changes in subsequent viral load counts.
ANNEX VII (D) V
IRAL LOAD RESULT FORM, AMPLICOR
HIV MONITORING, V1.5
Annex VII(d) - Viral Load Result Form,Amplicor HIV Monitoring,V1.5
VL-1 vvvv Lab Name
Lab Phone Number

Amplicor HIV Monitoring,version 1.5
Accession Number/Lab Registration Number : _________________________________________
Patient ID Number : ________________________________________________________________
Date Specimen Tested(dd/mm/yy):__________Date Of Report (dd/mm/yy):______________________
Test Kit Name : Amplicor HIV-1 Monitor Test ,Version 1.5 Manufacturer : ____________
Version : _______________________
Result
HIV-1 RNA Copies/ml
Notes : HIV-1 Quantization by amplicor HIV Monitor Test,Version 1.5

Interpretation : This procedure can detect virions associated HIV-1 RNA plasma at concentrations low as 50
RNA copies/ml to 750,000 HIV-1 RNA copies/mL.Low viral load values may occur as "False positives"and
that resemble HIV(e.g.HTLV).Therefore,caution must be exercised when such a result is obtained on a
Assays).
The minimum reliable and signicant change in measurement(as compared to baseline value /
status of the patient.The Amplicor HIV-1 Monitor test 1.5 is not intended to be used as a
dianostic test for hiv-1 infection.This test is not intended for HIV-2 Patients.
It is recommended that follow up viral load tests be repeted at the same laboratory with the same
technique/procedure in order to caompare changes in subsequent viral load .
ANNEX VIII
Process for External Quality Assessment for the laboratories performing
HIV-1 Viral Load Testing
Introduction
Process for External Quality Assessment for the laboratories performing HIV-1 Viral Load
Testing will include 4 surveys in a calendar year to the NACO identified centres for performing
HIV-1 Viral Load Testing for the Second line initiative.
This will serve as an important tool in the process of continuous quality improvement in
these laboratories.
Confidentiality
Participants will be given a Participant Number to be used as a reference in all correspondence.
At no time and under no circumstances is the identity of a participating laboratory revealed.
Report reviewers who assess results and provide comments/discussions and an educational
component for each report are unaware of the identity of participants.
Participating Laboratories:
Name of Laboratory & Contact Person of each participating lab would be provided to RCPA
EQAS coordinating laboratory in India
NACO has designated NARI to be the EQAS coordinating laboratory for VLEQAS in India.
NARI, Pune would take on the responsibility for ensuring that the EQAS programme
is successfully and regularly implemented with active participation of testing labs by
coordinating, monitoring, supervising, training, and providing troubleshooting support for
the VL EQAS runs held at regular quarterly intervals. Roche India would support NARI in
this activity and coordinate with RCPA Australia and the participating centers for all related
activities including but not limited to the delivery of the EQAS specimens to these labs for
proficiency testing four times a year at predetermined schedules. Roche India would also
provide coordination training and troubleshooting support to NARI as and when required
for the NACO VL labs in this entire activity. NARI would submit formal quarterly reports to
NACO on the performance of the NACO VL laboratories in the VLEQAS.
Testing
Participants should test specimens in the same manner as patient specimens.
(1) The specimens should be tested with the laboratorys regular patient workload by
personnel who routinely perform the testing in the laboratory.
(2) The participant should test specimens the same number of times that it routinely tests
patient specimens.
(3) The participant should maintain a copy of all records, including a copy of the completed
questionnaire, to record proficiency testing results.
(4) The results sheet should be signed by the analyst and the laboratory manager,
documenting that proficiency testing specimens were tested in the same manner
as patient specimens, the report reviewed, results discussed and action taken (if
appropriate). This documentation should be kept for a minimum of three years from the
date of the proficiency testing event.
Specimen Delivery
The survey panels will be sent to Roche Diagnostics India from RCPA Quality Program
Pvt. Limited, Australia in the frozen conditions
Upon arrival these panels would checked for the shipping conditions by an Authorized
person of Roche and supplemented with additional dry ice
4 surveys (1 survey per quarter) each consisting of 3 specimens will be sent out to
each participating laboratory each cycle of surveys.
The specimens will be sent out at the start of the survey and delivered by Roche
Diagnostics personnel to the individual laboratories to ensure ease of logistics and
that the specimen integrity is maintained.
Upon delivery, the specimens are to be frozen at -70C or -80C until the
appropriate questionnaire is received via email. It is essential that specimens are
frozen immediately upon receipt and stored in a freezer which is not a frost free
instrument or does not have a defrost cycle.
Specimens may contain virulent pathogens and must be treated with the same degree
of caution as routine diagnostic specimens. Specimens are issued to participants on
the understanding that they will be used for quality assurance purposes and that
they will be tested by staff trained to handle equivalent clinical specimens.
Survey Process
Receiveopen survey email alert from NACO
Participant to printsurvey Questionnaire
Test relevant survey specimens
Submit results via email directly to RCPA by the survey due date with a copy marked to NACO
RCPA will send the assessment report to the respective participating laboratory with a copy
marked to NACO
NARI Pune will submit to NACO formal reports quarterly on the EQAS performance of the
NACO viral load labs
Survey Questionnaires
Participants are given 18 days to perform testing and submit survey results.
Instructions are on each questionnaire explaining what is required. Please contact

the NARI if you do not understand any aspect of the questionnaire.
Feedback from participants is encouraged and a Compliments, Concerns,

Suggestions section is in each survey questionnaire, so that participants can
immediately provide feedback for specific surveys, as well as the overall Programme.
Disposal of Material
Any part of specimens which is not used by the participant shall be destroyed in the manner
required by any law or regulatory agency for the disposal of potentially bio-hazardous waste.
Late Return of Completed Questionnaires (Results)
Late results will delay report preparation. If a completed questionnaire arrives after all data
has been entered and collation of data has commenced, the received questionnaire will be
marked LATE and the final report to NARI from RCPA will not be amended to include these
late results.
Survey Reports
Survey reports are presented in the following format:-
Section One will contain a Participant Performance Table. This table identifies participants
returning results inconsistent with consensus of 80% of participating laboratories,
omission of kit details, use of expired kits, occurrence of transcription errors, inconsistent
or incomplete data, inappropriate interpretative comment selection and non identification
of clerical errors.
Section Two contains the collated report, which is a summary of participant results, and
includes discussion/comment from a scientist/pathologist with HIV expertise.
HIV RNA Quantitation (n=11) - Specimen 2A HIV RNA Quantitation (n=8) - Specimen 2B
5.5 6.5
5.0 6.0
4.5 5.5
Values (IU/mL Log10)
Values (IU/mL Log10)
5.0
4.0 4.5
3.5 4.0
3.0 3.5
2.5 3.0
2.0 2.5
1.5 2.0
1.0
Median
Range -0.25
1.5
1.0
Median
Range -0.25
0.5 Range +0.25
0.5 Range +0.25
Specimen 2A Specimen 2B
0.0 0.0
Participant Results Participant Results
ANNEXURE IX- SECOND LINE REPORTING
1 SL + AL: SACEP REGISTER FOR ALTERNATIVE FIRST LINE & SECOND LINE ART
(ADULTS AND CHILDREN)
(SACEP coordinator at CoE/pCoE and data manager at ART plus centre should maintain
this register)
These columns should be on left half of register
Month: Year:
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Name & Contact Number of NGOs linked to referring ART
Date of Referral (First electronic referral from ART centre
If Viral Load recommended, results (with date)/Grade of
Recommendations of SACEP (feedback to be sent to the

Whether VL testing recommended or not by SACEP (Y/N)
Latest CD4 (with date) at the time of SACEP assessment
Functional Status at time of SACEP assessment (WAB)

Appointment Given ( If Yes-Dates/If No Reason )
Clinical Staging at time of SACEP assessment

Contact Number
Centre (CCC/DLN/TI/other local NGOs)
Date of actual assessment by SACEP

Contact no. of referring ART Centre
Sl. No (SACEP registration No) #.
(not more than one month old))
referring ART centre& SACS) **

Name of referring ART Centre
ART Registration Number
seeking appointment)
Reason For Referral *

Patient Name
Care giver
Address
Gender
toxicity
Patient
Age

* 1. Suspected treatment failure 2. Side effects of drugs 3. On Second line ART from
Private 4. Others
** 1. Recommended for Second line ART 2. Substitution with PI containing regimen
3. Substitution of NRTI backbone 4. Substitution with other regimen (Specify
regimen code) 5. Management of complicated cases/others 6. Referred back to ART
centre for review after 1/3/6 months
*** 1. If viral load < 400 copies/ml, no OI, no side effects- transfer out the patient back
to the referring centre 2. if viral load> 400 copies/ml at 6 month after Second line ART
initiation and no OI/side effects, still transfer the patient to the referring centre and call
the patient back for viral load after another six months (12th month from the time of
initiation of Second line ART)
****For patients with viral load more than 400 copies/ml at Second viral load testing (at 6th month after Second line
ART initiation)
Date of initiation of Second line/Alternative
21
First line ART
Recommended regimen (indicate regimen
number as per NACO ART Guidelines) 22
Any Major OI observed while on Second line 23

ART

Date of viral load testing at 6 month after
24
initiation of Second line ART

Result of viral load testing at 6 months
25

Recommendations of the SACEP after Sec-
26
ond viral load ***

After initiation of Second line, whether Pa-
tient referred back to the referring ART centre
27
as per guidelines at sixth month (yes/no)

28
Date of referral back to the nodal ART centre

Viral load testing at 12 month( if recom-
Follow up of patients on Second line
29
mended by SACEP)****

Recommendations of SACEP at12th month
30
viral load, if applicable
National Guidelines on Second-line and Alternative First-line ART For Adults and Adolescents May 2013
1
2
3
These columns to be on the right side of the register
31
400- 5000 copies/ml)
4
5
Repeat Viral loads (with date) for
drugs at First SACEP review (As per
6
patients not eligible for Second line
guidelines, those whose VL is between
89
2 AL: ALTERNATIVE FIRST LINE FORMAT FOR SACEP MEETING (ADULT &
CHILDREN)
(To be prepared before SACEP meeting and given to all members during the
meeting and to be kept at CoE/pCoE/ART plus centre)
Meeting date :
1 2 3 4 5 6 7 8 9 10 11 12 13
CD4 counts
(within the program)
Type of toxicity /side

Name and address of
% Adherence to First
referring ART centre
(with date)
ART start date (out-
Clinical stage at the

time of assessment
Sl. No (SACEP regis-
side the program)

cells/Cmm
ART Registration
effects observed
Name of patient
ART start date

(expandable)
tration No).
line drugs

Number
Address
Gender
Age

Summary -2AL Alternative First line ART Members
Present
during the
SACEP
No of 1
Sl. No Name of the regimen patients
TDF containing regimen (Adult) 2
ATV/r based regimen (Adult) 3
LPV/r based regimen (adult) 4
Total number of patients ABC/3TC+NVP 5
reviewed by SACEP for
1 ABC/3TC+EFV
Alternative First line
treatment ABC/3TC+LPV/r
ZDV/3TC+LPV/r
d4T/3TC+LPV/r
TDF+3TC+ATV/r (HIV-2/dual toxicity)
TDF containing regimen (Adult)
ATV/r based regimen (Adult)
LPV/r based regimen (Adult)
Total number of patients ABC/3TC+NVP
2 actually recommended on
Alternative First line ART ABC/3TC+EFV
ABC/3TC+LPV/r
ZDV/3TC+LPV/r
d4T/3TC+LPV/r
Grade of toxicity
14
Photo documentation
15
(Yes/noO

Any OIs reported
16

Name of drug (d4t/AZT/
NVP or EFV or any other 17
ARV ) which (probably)
caused toxicity specify

Whether recommended
for Alt First line? (Yes/
18
No)

TDF based
19
Regimen

ATV/r
based
Adult Regimen
Regimen
Other regi-
men

ABC/3TC+
NVP

20
ABC/ 3TC+
EFV

ABC/ 3TC+
LPV/r

If recommended for Alt First line?
ZDV/ 3TC+
Paediatric Regimen
LPV/r
d4T/3TC+

LPV/r

Remarks
21
91
2 SL : SECOND LINE FORMAT FOR SACEP MEETING (ADULT & CHILDREN )
(To be prepared before every SACEP and given to members during the meeting &be
kept at CoE/pCoE/ART plus Centres)
Second line ART
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
CD4 counts
Viral Load result with date

Load Test by SACEP (Y/N)
(with date)
Sl. No (SACEP registration
Name , address of refer-
Whether recommended
Clinical Status (OI, Clini-
Recommended for Viral
no.
ART start date (outside
Adherence to First line

Cells/cmm all
ART start date (within
for Second line ART ?

values to be
the programme )
given
ART Registration
the programme)
Name of patient
ring ART centre
cal staging)
(Yes/No)
Remarks
Address
Gender
drugs
No).
Age
New cases

Follow up cases

New Cases: Those PLHIV who are being referred to SACEP for the First time and re-
referred cases who were previously not given appointment or were not previously eligible
(<400 copies/ml).
Follow up casesincludes:
Those PLHIV who have come for review with their First VL report or
Repeat VL results after initiation of Second line (6th/12th month) , or
T hose PLHIVs who were not eligible earlier and have come for review of repeat
viral loads results by SACEP (400- 5000 copies/ml)
2SL Summary -Second Line ART Members Present during the SACEP
No of 1
Sl. No patients
Total no. of patients referred to SACEP for 2
1
suspected treatment failure
Total no. of patients supposed to attend SACEP 3
2
for suspected treatment failure
Total Number of patients actually reviewed by 4
3
SACEP for suspected treatment failure
Total number of patients recommended for 5
4 Viral Load test
Total number of patients recommended for 6
5
Second Line ART (After VL)
Total number of patients actually initiated on
6 Second Line ART (After minimum 2 counselling
sessions)
94
3AL+SL COMBINED MONTHLY REPORTING FORMAT FOR SECOND & ALTERNATIVE FIRST LINE ART
(to be sent to NACO by 4th of every month to Secondline2008@gmail.com)
(Provided separately in Excel form)
artdrugs@gmail.com, Concerned SACS (JD, CST), RC & linked CoE/ART plus/pCoE)
1. Name of ART Centre
2. CMIS Code of ART centre (same as code for First line)
3. Name of the District
4. Name of the State
5. Name of Nodal Officer
6. Report for the period Month Year
Second line ART
Adult Children Total

7. Details of PLHIV referred to SACEP for suspected treatment failure
Male Female TS/TG Male Female
7.1 Cumulative number of PLHIV referred to SACEP for assessment at the
beginning of this month
7.2 Number of new PLHIV referred to SACEP for assessment during this
month
end of this month = 7.1 + 7.2
7.4a Cumulative number of patients referred from this CoE/ART plus centre
(The reporting centre) (out of 7.3)
7.4b Cumulative number of patients referred from referring ART centres
linked to this CoE /ART plus (out of 7.3)
7.4c Cumulative number of patients given appointment for SACEP review at
end of this month ( out of 7.3)
7.4d Cumulative number of patients actually reviewed by SACEP at end of
this month ( out of 7.4c)
7.4e Cumulative number of PLHIV found eligible for Viral Load (out of 7.4d)
7.4f Cumulative number of PLHIV actually underwent Viral Load (out of
7.4e)
8.1 Cumulative number of PLHIV found eligible for Second line at beginning
of this month
8.2 Number of PLHIV found eligible for Second line during this month
8.3 Cumulative number of PLHA found eligible for Second line at the end
of this month = 8.1 + 8.2
8.4 Cumulative number of patients ever started on Second line ART (Num-
ber at the beginning of this month) (8.7 of previous month)
8.5 Number of new patients started on Second line ART during this month
8.6 Number of patients restarted on Second line ART during this month
8.7 Cumulative number of patients ever started on Second line ART (Num-
ber at the end of this month) = 8.4+8.5+8.6
9.1 Cumulative number of patients on Second line who died since the
beginning of the programme
9.2a Cumulative number of patients on Second line who are transferred
out to other COE/ART plus
9.2b Cumulative number of patients on Second line who are transferred
out to the referring centres (ART centres)
9.2c Cumulative number of patients on Second line who are transferred
in ( from other COE/ART plus)
9.3 Number of all patients on Second line treatment whose treatment
status in this month is stopped treatment
9.4 Cumulative Number of patients on Second line who are lost to follow-up
(LFU)
9.5 Cumulative Number of patients on Second line treatment who did not
return to the ART centre (Defaulter)/whose treatment status is MIS in this
month
9.6 Total number of patients alive and on Second line ART (OT) at the end
of this month = 8.7+ 9.2c - (9.1+9.2a+9.3+9.4+9.5)
9.7a Out of 9.6, the number of patients on Second line ART initiated on
DOTS this month
95
96
9.7b Out of 9.6, the number of patients on Second line ART initiated on
non-DOTS anti-tuberculosis treatment this month
9.7c Out of 9.6, the total number of pregnant women on Second line ART
this month
beginning of this month
10.2 Number of new PLHIV referred to SACEP for assessment during this
month
end of this month(10.1+10.2)
10.3a Number referred from CoE/ART plus (The reporting centre) (out of
10.3)
10.3b Number referred from other ART centres (out of 10.3)
11.1 Cumulative number of PLHIV found eligible for Alternative First line
ART at beginning of this month (11.3 of previous month)
11.2 Number of PLHIV found eligible for Alternative First line ART during
this month
11.3 Total number of PLHIV found eligible for Alternative First line ART till
the end of this month(11.1+11.2)
12.1 Cumulative number of patients ever started on Alternative First line
ART (Number at the beginning of this month)
12.2 Number of new patients started on alternative First line ART during
this month
12.3 Cumulative number of patients ever started on Alternative First line
ART (Number at the end of this month) =12.1+12.2
13.1 Cumulative number of patients on alternate First line who died since
the beginning of the programme
13.2a Cumulative number of patients on Alternative First line who are
transferred out to other CoE/ART Plus Centres
13.2b Cumulative number of patients on Alternative First line who are
transferred out to the referring ART centre
13.2c Cumulative number of patients on Alternative First line who are
transferred in from other centres (CoE/ART plus)
13.3 The number of all patients on Alternative First line treatment whose
treatment status in this month is stopped treatment
13.4 Cumulative Number of patients receiving Alternative First line who are
lost to follow-up (LFU)
13.5 The number of patients on Alternative First line treatment who did not
return to the ART centre (Defaulter)/, whose treatment status is MIS in
this month
13.6 Total number of patients alive and on Alternative First line ART=
12.3+13.2c-(13.1+13.2a+13.3+13.4+13.5)
13.7 Out of 13.6, the number of patients on Alternative First line ART initi-
ated on DOTS this month
13.8 the number of patients on Alt First line ART initiated on non-DOTS
anti-tuberculosis treatment this month
13.9 the total number of pregnant women on Alternative First line ART this
month
14. Treatment Adherence Number
14.1a Of all patients who are on Second line ART this month (9.6), the number who have NOT been assessed for adherence
(refer guideline)
14.1b Of all patients on Second line ART (9.6) this month and who have been assessed for adherence, how many had 95%
adherence or better (refer guideline)
14.2a Of all patients who are on alternative First line ART this month (13.6) the number who have NOT been assessed for
adherence (refer guideline)
14.2b Of all patients on alternative First line ART (13.6) this month and who have been assessed for adherence, how many
had 95% adherence or better (refer guideline)
15 a. Primary Regimen of PLHIV started on Second line/Alternative First line ART at the end of the month
Regimen Adult Pediatrics Total
Tenofovir+ Lamivudine + Nevirapine 1 1 2
Tenofovir + Lamivudine + Efavirenz 1 1 2
Zidovudine + Lamivudine + Atazanavir/Ritonavir 1 1 2
Zidovudine + Lamivudine + Lopinavir/Ritonavir 1 1 2
Tenofovir + Lamivudine+ Atazanavir/Ritonavir 1 1 2
97
98
Tenofovir + Lamivudine +Lopinavir/Ritonavir 1 1 2
Stavudine + Lamivudine + Lopinavir/Ritonavir 1 1 2

Stavudine + Lamivudine + Atazanavir/Ritonavir 1 1 2
Abacavir + Lamivudine + Nevirapine 1 1 2
Abacavir + Lamivudine + Efavirenz 1 1 2
Abacavir + Lamivudine + Lopinavir/Ritonavir 1 1 2
Zidovudine + Lamivudine + Lopinavir/Ritnovir 1 1 2
Stavudine + Lamivudine + Lopinavir/Ritonavir 1 1 2
Abacavir + Lamivudine + Didanosine + Lopinavir/Ritonavir 1 1 2

Others 1 1 2
Total 15 15 30
15.b. Total Number of Patients on CPT Prophylaxis

Regimen Adults Pediatrics
Cotrimoxazole (DS)
Cotrimoxazole (SS)
Cotrimoxazole Suspension
Total number of patients
15.c. Opportunistic Infections
OIs Number of episodes of OIs this OIs Number of episodes of OIs this month
month
Adults Pediatrics Adults Pediatrics
1(a) Tuberculosis (Pulmonary) 8 Toxoplasmosis

1(b)Tuberculosis (Extra-Pulmo- 9 CMV Retinitis
nary)
2 Candidiasis 10 Bacterial
Infections(skin)
3 Diarrhoea 11 Herpes Simplex
4 PCP 12 Malignancy
5 Herpes Zoster 13 Others
6 Bacterial Infections (Respiratory) 14 Others
7 Cryptococcal Meningitis
99
100
15.d Were there any specific side effects noted for Second line/Alternative First line ART during the month
Male Female
Particulars Adult Pediatrics Adult
1. AZT Induced Anaemia
2. Peripheral Neuropathy
3. Hepatitis
4. Lipodystrophy

5.Pancreatitis
6. Skin Reaction
7. CNS Side Effects
8. IRIS
4 AL : LIST OF PATIENTS ON ALTERNATIVE FIRST LINE ART
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Type of Toxicity To be filled by CoE/PCoE/ART plus

centre only
Clinical Laboratory Patient referred Date of refer-
Sex
Age
Name
count
Symptoms tests
Address
back to the ral back to the
(1st line)
Telephone
mendations
Current CD4
ART Reg. No.
Sl. No (SACEP
SACEP recom-
Date of ART start
Probable drug
line Regimen*
referring ART referring ART

causing toxicity
Alternative First
registration No).
Date of ART start
(alternative First line)
Status of patient (OT/
MIS/LFU/TO/Death)
centre (yes/no?) centre

4 SL : LIST OF PATIENTS ON SECOND LINE ART
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
CD4 Viral load at the time SACEP recommendations
count of SACEP assessment To be filled by
with date CoE/PCoE/ART
plus centre only
After 6 After 12 After 6 After Patient
months months months 12 re-
on 2nd on 2nd on 2nd months ferred
Date of
Line Line Line on 2nd back
referral
Line to the
back to
refer-
the refer-
ring
ring ART
ART
centre
centre
(yes/
Sr. No.( (SACEP Regn. No)

ART Reg. No.
Name
Age
Sex
Address
Telephone
Date of ART start (1st line)
Current regimen (at the time of SACEP
Referral)
Baseline
At the time of At the time of
referral to SACEP
Baseline
After Baseline VL
Date of ART start (Second line)
Second line ART regimen initiated
Status of patient (OT/MIS/LFU/TO/
Death)
no?)
1
2
3
4
5
6
7
8
9
10
Total
101
102
5 SL: CENTRE WISE (LINKED CENTRE INFORMATION) BREAK UP FOR PLHIV INITIATED ON SECOND LINE ART
S. No Names Cumula- Cumula- Cumula- Cumula- Cumulative Cumu- Cumulative Cumu- Alive and on Second line ART (9.6)
of tive no of tive no of tive no of tive no of number of lative number of lative
Linked patients patients patients patients PLHIV actually number patients ever number of
ART Referred given ap- actually eligible for underwent of PLHA started on patients
Centres to SACEP pointment reviewed viral load Viral Load found Second line on Second At CoE/ At refer- Total
(7.3) for SACEP by SACEP test (7.4e) (7.4f) eligible for ART (8.7) line who ART plus ring centre
review (7.4d) Second died (9.1) centre
(7.4c) line (8.3)
1
2
3
4
5
6
7
8
9
10
Total
ANNEX X
ACKNOWLEDGEMENTS
The National AIDS Control organisation wishes to acknowledge contributions made
by the guidelines team at NACO, Regional Coordinators, Joint Directors of SACS,
Program Directors of CoEs, and other contributors in updating these guidelines.
We also acknowledge the technical support provided by World Health Organisation

country office for India in developing and updating these 2013 guidelines.
The support of International Training and Education Centre for Health (I-TECH),
India for printing these guidelines is also acknowledged

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Table of Contents

1.1 First LINE & Second LINE ART REGIMEN:

1.2 SUBSTITUTION VS. SWITCH

Change of ARVs prescribed should be carefully distinguished between substituting a

Treatment Failure refers to the loss of antiviral efficacy to current regimen

Table 1: NACO Approved ART regimen

Regimen ARV Drug Combinations Indications

Stavudine+ Lamivudine+ For patients on Regimen V who develop severe Atazanavir

1.3 ALTERNATIVE ARV DRUGS FOR INTOLERANCE TO ZDV/TDF AND NVP/EFV:

Regimen Toxicity Drug substitution

Table 3: Substituting with alternative First Line ARV drugs

First line ARV causing the toxicity Alternative substitute Remarks

(a) Intolerance to both TDF and AZT

TDF + 3TC d4T + 3TC Continue the same NNRTI

(c) Intolerance to TDF, d4T and AZT

See Annex I: Severity grading of clinical and laboratory toxicities of ARVs

Adherence support and monitoring to ensure >95% adherence:

Table 4: Clinical staging events to guide decision making on switching

1.5 IDENTIFYING TREATMENT FAILURE

High index of suspicion is required

Clinical failure (i) New or recurrent WHO stage 4 condition, after at

i. Current event must be differentiated from IRIS.

Assess adherence and support patient to improve this (reinforce)

Screen and treat intercurrent OIs, exclude IRIS

Provide Cotrimoxazole based on CD4 or clinical stage immediately

If TB is present: assess if this is re infection or IRIS or a new infection. If the response

1) It is important to differentiate between complications of HIV disease and ARV

4) As a general principle, mild toxicities do not require discontinuation of ART or

5) Moderate to severe toxicities require substitution with a different drug of same

6) Severe life threatening toxicities e.g. Stevens Johnson syndrome require

Suspect treatment failure during the medical consultation on following ground:

Patient has NO Signs or symptoms of OI

Most recent CD4 Repeat CD4 immediately

Does CD4 value

Review need for OI prophylaxis/treatment especially CPT

Eligibility for enrollment into Second Line Treatment:

In the meanwhile, the patient is to be counseled for 100% adherence in a few

After review of patient records by the SACEP coordinator/research fellow/SMO,

o Provide 2nd line ART

o Not eligible for 2nd line ART

o Continue First line, reinforce adherence and re-evaluate

o Evaluate for HIV 2

Suspect treatment failure by clinical and/or CD4 criteria

Viral load test

No change in 1st No change in 1st Virologically confirmed treatment failure.

The objective of the Second-line is:

To prolong survival of the PLHIV

Table 6: NACO Second Line Regimen:

ARV drugs for

ARV drug Side effect/toxicity Management

Side effects may include cough, diarrhea,

1.9 DRUG INTERACTION:

Avoid concurrent use of the following drugs:

Astemizole, Cisapride, Fluticasone, Indinavir, Lovastatin, Simvastatin, Midazolam,

Unique drug interaction involving Atazanavir:

2. Give ATV 300 mg + RTV 100 mg simultaneously with

Example:If a PLHIV onZidovudine + Lamivudine + Ata-

2. PPIs should not exceed the dose of Omeprazole

3. PPIs are not recommended in PI-experienced

Example: If a PLHIV is onTenofovir + Lamivudine +

b. Atazanavir induced urolithiasis is also reported; presumably due to precipitation of the

Important consideration in pregnancy

1.10 SECOND-LINE ART AND TB TREATMENT

1.3 ALTERNATIVE ARV DRUGS FOR INTOLERANCE TO ZDV/TDF AND NVP/EFV:

2.4 TOR OF ADDITIONAL MANPOWER: SACEP COORDINATOR

3.1 INSTRUCTIONS FOR MONITORING/RECORDS KEEPING FOR SECOND

4.5 SPECIMEN COLLECTION, STORAGE, AND TRANSPORTATION:

4.5.5 PROCESSING OF THE WHOLE BLOOD SPECIMEN IN THE RECEIVING LAB:

4.6 FACTORS TO BE CONSIDERED WHILE INTERPRETING THE VIRAL LOAD